Liquid biopsy at the frontier of detection, prognosis and progression monitoring in colorectal cancer

Hui Zhou, Liyong Zhu, Jun Song, Guohui Wang, Pengzhou Li, Weizheng Li, Ping Luo, Xulong Sun, Jin Wu, Yunze Liu, Shaihong Zhu, Yi Zhang, Hui Zhou, Liyong Zhu, Jun Song, Guohui Wang, Pengzhou Li, Weizheng Li, Ping Luo, Xulong Sun, Jin Wu, Yunze Liu, Shaihong Zhu, Yi Zhang

Abstract

Colorectal cancer (CRC) is one of the most common cancers worldwide and a leading cause of carcinogenic death. To date, surgical resection is regarded as the gold standard by the operator for clinical decisions. Because conventional tissue biopsy is invasive and only a small sample can sometimes be obtained, it is unable to represent the heterogeneity of tumor or dynamically monitor tumor progression. Therefore, there is an urgent need to find a new minimally invasive or noninvasive diagnostic strategy to detect CRC at an early stage and monitor CRC recurrence. Over the past years, a new diagnostic concept called "liquid biopsy" has gained much attention. Liquid biopsy is noninvasive, allowing repeated analysis and real-time monitoring of tumor recurrence, metastasis or therapeutic responses. With the advanced development of new molecular techniques in CRC, circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), exosomes, and tumor-educated platelet (TEP) detection have achieved interesting and inspiring results as the most prominent liquid biopsy markers. In this review, we focused on some clinical applications of CTCs, ctDNA, exosomes and TEPs and discuss promising future applications to solve unmet clinical needs in CRC patients.

Keywords: Circulating tumor DNA; Circulating tumor cells; Clinical application; Colorectal cancer; Exosomes; Liquid biopsy; Tumor-educated platelets.

Conflict of interest statement

The authors declare that they have no competing interests.

© 2022. The Author(s).

Figures

Fig. 1
Fig. 1
Liquid biopsy in CRC patients. CTCs, ctDNA, exosomes, CTECs, TEPs can all be detected by blood samples collected for liquid biopsy. Their analyses can be used to help with molecular profiling and treatment selection. CTCs can also be employed for culture and xenografting to help in CRC treatment selection
Fig. 2
Fig. 2
Timeline of key discoveries of liquid biopsy
Fig. 3
Fig. 3
Technologies for CTC and ctDNA enrichment, detection and clinical application. A CTCs are preliminary enriched from whole blood sample via different enrichment techniques. Different detection technologies can help with early detection, prognostication, chemotherapy, target therapy of CRC patients. B ctDNA are detected from whole blood sample via targeted and untargeted approaches. ctDNA can supported with early diagnosis, prognosis, disease monitoring and detected the gene mutations of CRC patients. C Exosomes are enriched from whole blood sample via different enrichment techniques. Different detection technologies can help with diagnosis, prognosis, disease monitoring, therapy of CRC patients. D TEPs are detected from whole blood sample via different approaches. TEPs can supported with early cancer detection, diagnosis, and disease monitoring of CRC patients. E CTECs are detected via different approaches. CTECs can supported with early cancer detection, diagnosis and prognosis, antiangiogenic therapy of CRC patients

References

    1. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global Cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71:209–249.
    1. Arnold M, Sierra MS, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global patterns and trends in colorectal cancer incidence and mortality. Gut. 2017;66:683–691.
    1. Pantel K, Alix-Panabières C. Circulating tumour cells in cancer patients: challenges and perspectives. Trends Mol Med. 2010;16:398–406.
    1. Lianidou ES, Mavroudis D, Sotiropoulou G, Agelaki S, Pantel K. What's new on circulating tumor cells? A meeting report. Breast Cancer Res. 2010;12:307–307.
    1. Alix-Panabieres C, Pantel K. Circulating tumor cells: liquid biopsy of Cancer. Clin Chem. 2013;59:110–118.
    1. Ashworth T. A case of cancer in which cells similar to those in the tumours were seen in the blood after death. Aust Med J. 1869;14:146–149.
    1. Cristofanilli M, Budd GT, Ellis MJ, Stopeck A, Matera J, Miller MC, Reuben JM, Doyle GV, Allard WJ, Terstappen LW, Hayes DF. Circulating tumor cells, disease progression, and survival in metastatic breast cancer. N Engl J Med. 2004;351:781–791.
    1. Röcken M. Early tumor dissemination, but late metastasis: insights into tumor dormancy. J Clin Invest. 2010;120:1800–1803.
    1. Pierga JY, Hajage D, Bachelot T, Delaloge S, Brain E, Campone M, Diéras V, Rolland E, Mignot L, Mathiot C, Bidard FC. High independent prognostic and predictive value of circulating tumor cells compared with serum tumor markers in a large prospective trial in first-line chemotherapy for metastatic breast cancer patients. Ann Oncol. 2012;23:618–624.
    1. Lohr JG, Adalsteinsson VA, Cibulskis K, Choudhury AD, Rosenberg M, Cruz-Gordillo P, Francis JM, Zhang CZ, Shalek AK, Satija R, et al. Whole-exome sequencing of circulating tumor cells provides a window into metastatic prostate cancer. Nat Biotechnol. 2014;32:479–484.
    1. Jiang R, Lu YT, Ho H, Li B, Chen JF, Lin M, Li F, Wu K, Wu H, Lichterman J, et al. A comparison of isolated circulating tumor cells and tissue biopsies using whole-genome sequencing in prostate cancer. Oncotarget. 2015;6:44781–44793.
    1. Mandel P, Metais P. Nuclear acids in human blood plasma. C R Seances Soc Biol Fil. 1948;142:241–243.
    1. Leon SA, Shapiro B, Sklaroff DM, Yaros MJ. Free DNA in the serum of cancer patients and the effect of therapy. Cancer Res. 1977;37:646–650.
    1. Caldas C, Hahn SA, Hruban RH, Redston MS, Yeo CJ, Kern SE. Detection of K-ras mutations in the stool of patients with pancreatic adenocarcinoma and pancreatic ductal hyperplasia. Cancer Res. 1994;54:3568–3573.
    1. Esteller M, Sanchez-Cespedes M, Rosell R, Sidransky D, Baylin SB, Herman JG. Detection of aberrant promoter hypermethylation of tumor suppressor genes in serum DNA from non-small cell lung cancer patients. Cancer Res. 1999;59:67–70.
    1. Diehl F, Schmidt K, Choti MA, Romans K, Goodman S, Li M, Thornton K, Agrawal N, Sokoll L, Szabo SA, et al. Circulating mutant DNA to assess tumor dynamics. Nat Med. 2008;14:985–990.
    1. S ELA, Mäger I, Breakefield XO, Wood MJ: extracellular vesicles: biology and emerging therapeutic opportunities. Nat Rev Drug Discov. 2013;12:347–57.
    1. Johnstone RM, Adam M, Hammond JR, Orr L, Turbide C. Vesicle formation during reticulocyte maturation. Association of plasma membrane activities with released vesicles (exosomes) J Biol Chem. 1987;262:9412–9420.
    1. Raposo G, Nijman HW, Stoorvogel W, Liejendekker R, Harding CV, Melief CJ, Geuze HJ. B lymphocytes secrete antigen-presenting vesicles. J Exp Med. 1996;183:1161–1172.
    1. Zitvogel L, Regnault A, Lozier A, Wolfers J, Flament C, Tenza D, Ricciardi-Castagnoli P, Raposo G, Amigorena S. Eradication of established murine tumors using a novel cell-free vaccine: dendritic cell-derived exosomes. Nat Med. 1998;4:594–600.
    1. Kalluri R, LeBleu VS. The biology, function, and biomedical applications of exosomes. Science. 2020;367(6478):eaau6977.
    1. George JN. Platelets. Lancet. 2000;355:1531–1539.
    1. van der Meijden PEJ, Heemskerk JWM. Platelet biology and functions: new concepts and clinical perspectives. Nat Rev Cardiol. 2019;16:166–179.
    1. McAllister SS, Weinberg RA. The tumour-induced systemic environment as a critical regulator of cancer progression and metastasis. Nat Cell Biol. 2014;16:717–727.
    1. Trousseau A. Clinique medicale de l'hotel Dieu de Paris quatrieme edition. Medical clinic at Dieu's hotel in Paris. 1873;3.
    1. Wright JH. The origin and nature of the blood plates. Boston Med Surg J. 1906;154:643–645.
    1. Nilsson RJ, Balaj L, Hulleman E, van Rijn S, Pegtel DM, Walraven M, Widmark A, Gerritsen WR, Verheul HM, Vandertop WP, et al. Blood platelets contain tumor-derived RNA biomarkers. Blood. 2011;118:3680–3683.
    1. Best MG, Sol N, Kooi I, Tannous J, Westerman BA, Rustenburg F, Schellen P, Verschueren H, Post E, Koster J, et al. RNA-Seq of tumor-educated platelets enables blood-based Pan-Cancer, multiclass, and molecular pathway Cancer diagnostics. Cancer Cell. 2015;28:666–676.
    1. Pantel K, Speicher MR. The biology of circulating tumor cells. Oncogene. 2016;35:1216–1224.
    1. Tsai WS, You JF, Hung HY, Hsieh PS, Hsieh B, Lenz HJ, Idos G, Friedland S, Yi-Jiun Pan J, Shao HJ, et al. Novel circulating tumor cell assay for detection of colorectal adenomas and Cancer. Clin Transl Gastroenterol. 2019;10:e00088.
    1. Bork U, Rahbari NN, Schölch S, Reissfelder C, Kahlert C, Büchler MW, Weitz J, Koch M. Circulating tumour cells and outcome in non-metastatic colorectal cancer: a prospective study. Br J Cancer. 2015;112:1306–1313.
    1. Hinz S, Röder C, Tepel J, Hendricks A, Schafmayer C, Becker T, Kalthoff H. Cytokeratin 20 positive circulating tumor cells are a marker for response after neoadjuvant chemoradiation but not for prognosis in patients with rectal cancer. BMC Cancer. 2015;15:953.
    1. Pan RJ, Hong HJ, Sun J, Yu CR, Liu HS, Li PY, Zheng MH. Detection and clinical value of circulating tumor cells as an assisted prognostic marker in colorectal Cancer patients. Cancer Manag Res. 2021;13:4567–4578.
    1. Abdalla TSA, Meiners J, Riethdorf S, König A, Melling N, Gorges T, Karstens KF, Izbicki JR, Pantel K, Reeh M. Prognostic value of preoperative circulating tumor cells counts in patients with UICC stage I-IV colorectal cancer. PLoS One. 2021;16:e0252897.
    1. Tan Y, Wu H. The significant prognostic value of circulating tumor cells in colorectal cancer: a systematic review and meta-analysis. Curr Probl Cancer. 2018;42:95–106.
    1. Groot Koerkamp B, Rahbari NN, Büchler MW, Koch M, Weitz J. Circulating tumor cells and prognosis of patients with resectable colorectal liver metastases or widespread metastatic colorectal cancer: a meta-analysis. Ann Surg Oncol. 2013;20:2156–2165.
    1. Connor AA, McNamara K, Al-Sukhni E, Diskin J, Chan D, Ash C, Lowes LE, Allan AL, Zogopoulos G, Moulton CA, Gallinger S. Central, but not peripheral, circulating tumor cells are prognostic in patients undergoing resection of colorectal Cancer liver metastases. Ann Surg Oncol. 2016;23:2168–2175.
    1. Zhao JX, Liu LR, Yang XY, Liu F, Zhang ZG. Serum CA19-9 as a marker of circulating tumor cells in first reflux blood of colorectal cancer patients. Oncotarget. 2017;8:67918–67932.
    1. Wu F, Zhu J, Mao Y, Li X, Hu B, Zhang D. Associations between the epithelial-mesenchymal transition phenotypes of circulating tumor cells and the Clinicopathological features of patients with colorectal Cancer. Dis Markers. 2017;2017:9474532.
    1. Zhong Y, Ma T, Qiao T, Hu H, Li Z, Luo K, Wang Y, Tang Q, Wang G, Huang R, Wang X. Role of phenotypes of circulating tumor cells in the diagnosis and treatment of colorectal Cancer. Cancer Manag Res. 2021;13:7077–7085.
    1. Le DT, Durham JN, Smith KN, Wang H, Bartlett BR, Aulakh LK, Lu S, Kemberling H, Wilt C, Luber BS, et al. Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade. Science. 2017;357:409–413.
    1. Gandara DR, Paul SM, Kowanetz M, Schleifman E, Zou W, Li Y, Rittmeyer A, Fehrenbacher L, Otto G, Malboeuf C, et al. Blood-based tumor mutational burden as a predictor of clinical benefit in non-small-cell lung cancer patients treated with atezolizumab. Nat Med. 2018;24:1441–1448.
    1. Toor SM, Murshed K, Al-Dhaheri M, Khawar M, Abu Nada M, Elkord E. Immune checkpoints in circulating and tumor-infiltrating CD4(+) T cell subsets in colorectal Cancer patients. Front Immunol. 2019;10:2936.
    1. Borghaei H, Paz-Ares L, Horn L, Spigel DR, Steins M, Ready NE, Chow LQ, Vokes EE, Felip E, Holgado E, et al. Nivolumab versus Docetaxel in advanced nonsquamous non-small-cell lung Cancer. N Engl J Med. 2015;373:1627–1639.
    1. Le DT, Uram JN, Wang H, Bartlett BR, Kemberling H, Eyring AD, Skora AD, Luber BS, Azad NS, Laheru D, et al. PD-1 blockade in tumors with mismatch-repair deficiency. N Engl J Med. 2015;372:2509–2520.
    1. Fuchs CS, Doi T, Jang RW, Muro K, Satoh T, Machado M, Sun W, Jalal SI, Shah MA, Metges JP, et al. Safety and efficacy of Pembrolizumab monotherapy in patients with previously treated advanced gastric and Gastroesophageal junction Cancer: phase 2 clinical KEYNOTE-059 trial. JAMA Oncol. 2018;4:e180013.
    1. Satelli A, Batth IS, Brownlee Z, Rojas C, Meng QH, Kopetz S, Li S. Potential role of nuclear PD-L1 expression in cell-surface vimentin positive circulating tumor cells as a prognostic marker in cancer patients. Sci Rep. 2016;6:28910.
    1. Raimondi L, Raimondi FM, Di Benedetto L, Cimino G, Spinelli GP. PD-L1 Expression on Circulating Tumour Cells May Be Predictive of Response to Regorafenib in Patients Diagnosed with Chemorefractory Metastatic Colorectal Cancer. Int J Mol Sci. 2020;21:6907.
    1. Songdong Meng DT, Eugene P. Frenkel: circulating tumor cells in patients with breast cancer dormancy. Clin Cancer Res. 2004;10:8152–8162.
    1. Kowalik A, Kowalewska M, Góźdź S. Current approaches for avoiding the limitations of circulating tumor cells detection methods-implications for diagnosis and treatment of patients with solid tumors. Transl Res. 2017;185:58–84.e15.
    1. Yin CQ, Yuan CH, Qu Z, Guan Q, Chen H, Wang FB. Liquid biopsy of hepatocellular carcinoma: circulating tumor-derived biomarkers. Dis Markers. 2016;2016:1427849.
    1. Racila E, Euhus D, Weiss AJ, Rao C, McConnell J, Terstappen LWMM, Uhr JW. Detection and characterization of carcinoma cells in the blood. Proc Natl Acad Sci. 1998;95:4589–4594.
    1. Rushton AJ, Nteliopoulos G, Shaw JA, Coombes RC. A review of circulating tumour cell enrichment technologies. Cancers. 2021;13:970.
    1. Bahnassy AA, Salem SE, Mohanad M, Abulezz NZ, Abdellateif MS, Hussein M, Zekri CAN, Zekri AN, Allahloubi NMA. Prognostic significance of circulating tumor cells (CTCs) in Egyptian non-metastatic colorectal cancer patients: A comparative study for four different techniques of detection (Flowcytometry, Cell Search, Quantitative Real-time PCR and Cytomorphology) Exp Mol Pathol. 2019;106:90–101.
    1. Nagrath S, Sequist LV, Maheswaran S, Bell DW, Irimia D, Ulkus L, Smith MR, Kwak EL, Digumarthy S, Muzikansky A, et al. Isolation of rare circulating tumour cells in cancer patients by microchip technology. Nature. 2007;450:1235–1239.
    1. Sarioglu AF, Aceto N, Kojic N, Donaldson MC, Zeinali M, Hamza B, Engstrom A, Zhu H, Sundaresan TK, Miyamoto DT, et al. A microfluidic device for label-free, physical capture of circulating tumor cell clusters. Nat Methods. 2015;12:685–691.
    1. Li W, Wang H, Zhao Z, Gao H, Liu C, Zhu L, Wang C, Yang Y. Emerging nanotechnologies for liquid biopsy: the detection of circulating tumor cells and extracellular vesicles. Adv Mater. 2019;31:e1805344.
    1. Wang R, Chu GCY, Mrdenovic S, Annamalai AA, Hendifar AE, Nissen NN, Tomlinson JS, Lewis M, Palanisamy N, Tseng HR, et al. Cultured circulating tumor cells and their derived xenografts for personalized oncology. Asian J Urol. 2016;3:240–253.
    1. Muluhngwi P, Valdes R, Jr, Fernandez-Botran R, Burton E, Williams B, Linder MW. Cell-free DNA diagnostics: current and emerging applications in oncology. Pharmacogenomics. 2019;20:357–380.
    1. Spindler KG. Methodological, biological and clinical aspects of circulating free DNA in metastatic colorectal cancer. Acta Oncol. 2017;56:7–16.
    1. Vymetalkova V, Cervena K, Bartu L, Vodicka P. Circulating Cell-Free DNA and Colorectal Cancer: A Systematic Review. Int J Mol Sci. 2018;19:3356.
    1. Yang Y-C, Wang D, Jin L, Yao H-W, Zhang J-H, Wang J, Zhao X-M, Shen C-Y, Chen W, Wang X-L, et al. Circulating tumor DNA detectable in early- and late-stage colorectal cancer patients. Biosci Rep. 2018;38:BSR20180322.
    1. Reinert T, Henriksen TV, Christensen E, Sharma S, Salari R, Sethi H, Knudsen M, Nordentoft I, Wu HT, Tin AS, et al. Analysis of plasma cell-free DNA by Ultradeep sequencing in patients with stages I to III colorectal Cancer. JAMA Oncol. 2019;5:1124–1131.
    1. Tie J, Cohen JD, Wang Y, Christie M, Simons K, Lee M, Wong R, Kosmider S, Ananda S, McKendrick J, et al. Circulating tumor DNA analyses as markers of recurrence risk and benefit of adjuvant therapy for stage III Colon Cancer. JAMA Oncol. 2019;5:1710–1717.
    1. Phallen J, Sausen M, Adleff V, Leal A, Hruban C, White J, Anagnostou V, Fiksel J, Cristiano S, Papp E, et al. Direct detection of early-stage cancers using circulating tumor DNA. Sci Transl Med. 2017;9:eaan2415.
    1. Agah S, Akbari A, Talebi A, Masoudi M, Sarveazad A, Mirzaei A, Nazmi F. Quantification of plasma cell-free circulating DNA at different stages of colorectal Cancer. Cancer Investig. 2017;35:625–632.
    1. Bedin C, Enzo MV, Del Bianco P, Pucciarelli S, Nitti D, Agostini M. Diagnostic and prognostic role of cell-free DNA testing for colorectal cancer patients. Int J Cancer. 2017;140:1888–1898.
    1. Kobayashi S, Nakamura Y, Taniguchi H, Odegaard JI, Nomura S, Kojima M, Sugimoto M, Konishi M, Gotohda N, Takahashi S, Yoshino T. Impact of preoperative circulating tumor DNA status on survival outcomes after hepatectomy for Resectable colorectal liver metastases. Ann Surg Oncol. 2021;28:4744–4755.
    1. Tie J, Wang Y, Cohen J, Li L, Hong W, Christie M, Wong HL, Kosmider S, Wong R, Thomson B, et al. Circulating tumor DNA dynamics and recurrence risk in patients undergoing curative intent resection of colorectal cancer liver metastases: a prospective cohort study. PLoS Med. 2021;18:e1003620.
    1. Van't Erve I, Rovers KP, Constantinides A, Bolhuis K, Wassenaar EC, Lurvink RJ, Huysentruyt CJ, Snaebjornsson P, Boerma D, van den Broek D, et al. Detection of tumor-derived cell-free DNA from colorectal cancer peritoneal metastases in plasma and peritoneal fluid. J Pathol Clin Res. 2021;7:203–208.
    1. Yu H, Han L, Yuan J, Sun Y. Circulating tumor cell free DNA from plasma and urine in the clinical management of colorectal cancer. Cancer Biomark. 2020;27:29–37.
    1. Laird PW, Jaenisch R. The role of DNA methylation in cancer genetic and epigenetics. Annu Rev Genet. 1996;30:441–464.
    1. Luo H, Zhao Q, Wei W, Zheng L, Yi S, Li G, Wang W, Sheng H, Pu H, Mo H, et al. Circulating tumor DNA methylation profiles enable early diagnosis, prognosis prediction, and screening for colorectal cancer. Sci Transl Med. 2020;12:eaax7533.
    1. Nassar FJ, Msheik ZS, Nasr RR, Temraz SN. Methylated circulating tumor DNA as a biomarker for colorectal cancer diagnosis, prognosis, and prediction. Clin Epigenetics. 2021;13:111.
    1. Jin S, Zhu D, Shao F, Chen S, Guo Y, Li K, Wang Y, Ding R, Gao L, Ma W, et al. Efficient detection and post-surgical monitoring of colon cancer with a multi-marker DNA methylation liquid biopsy. Proc Natl Acad Sci U S A. 2021;1188:e2017421118.
    1. Bach S, Paulis I, Sluiter NR, Tibbesma M, Martin I, van de Wiel MA, Tuynman JB, Bahce I, Kazemier G, Steenbergen RDM. Detection of colorectal cancer in urine using DNA methylation analysis. Sci Rep. 2021;11:2363.
    1. Thomsen CB, Hansen TF, Andersen RF, Lindebjerg J, Jensen LH, Jakobsen A. Early identification of treatment benefit by methylated circulating tumor DNA in metastatic colorectal cancer. Ther Adv Med Oncol. 2020;12:1758835920918472.
    1. Liu L, Toung JM, Jassowicz AF, Vijayaraghavan R, Kang H, Zhang R, Kruglyak KM, Huang HJ, Hinoue T, Shen H, et al. Targeted methylation sequencing of plasma cell-free DNA for cancer detection and classification. Ann Oncol. 2018;29:1445–1453.
    1. Wu X, Zhang Y, Hu T, He X, Zou Y, Deng Q, Ke J, Lian L, He X, Zhao D, et al. A novel cell-free DNA methylation-based model improves the early detection of colorectal cancer. Mol Oncol. 2021;15:2702–2714.
    1. Barault L, Amatu A, Siravegna G, Ponzetti A, Moran S, Cassingena A, Mussolin B, Falcomatà C, Binder AM, Cristiano C, et al. Discovery of methylated circulating DNA biomarkers for comprehensive non-invasive monitoring of treatment response in metastatic colorectal cancer. Gut. 2018;67:1995–2005.
    1. Church TR, Wandell M, Lofton-Day C, Mongin SJ, Burger M, Payne SR, Castaños-Vélez E, Blumenstein BA, Rösch T, Osborn N, et al. Prospective evaluation of methylated SEPT9 in plasma for detection of asymptomatic colorectal cancer. Gut. 2014;63:317–325.
    1. deVos T, Tetzner R, Model F, Weiss G, Schuster M, Distler J, Steiger KV, Grützmann R, Pilarsky C, Habermann JK, et al. Circulating methylated SEPT9 DNA in plasma is a biomarker for colorectal cancer. Clin Chem. 2009;55:1337–1346.
    1. Warren JD, Xiong W, Bunker AM, Vaughn CP, Furtado LV, Roberts WL, Fang JC, Samowitz WS, Heichman KA. Septin 9 methylated DNA is a sensitive and specific blood test for colorectal cancer. BMC Med. 2011;9:133.
    1. Fakih MG. Metastatic colorectal cancer: current state and future directions. J Clin Oncol. 2015;33:1809–1824.
    1. Yu IS, Cheung WY. Metastatic colorectal Cancer in the era of personalized medicine: a more tailored approach to systemic therapy. Can J Gastroenterol Hepatol. 2018;2018:9450754.
    1. Schraa SJ, van Rooijen KL, van der Kruijssen DEW, Rubio Alarcón C, Phallen J, Sausen M, Simmons J, Coupé VMH, van Grevenstein WMU, Elias S, et al. Circulating tumor DNA guided adjuvant chemotherapy in stage II colon cancer (MEDOCC-CrEATE): study protocol for a trial within a cohort study. BMC Cancer. 2020;20:790.
    1. Taniguchi H, Nakamura Y, Kotani D, Yukami H, Mishima S, Sawada K, Shirasu H, Ebi H, Yamanaka T, Aleshin A, et al. CIRCULATE-Japan: circulating tumor DNA-guided adaptive platform trials to refine adjuvant therapy for colorectal cancer. Cancer Sci. 2021;112:2915–2920.
    1. French AJ, Sargent DJ, Burgart LJ, Foster NR, Kabat BF, Goldberg R, Shepherd L, Windschitl HE, Thibodeau SN. Prognostic significance of defective mismatch repair and BRAF V600E in patients with colon cancer. Clin Cancer Res. 2008;14:3408–3415.
    1. Misale S, Yaeger R, Hobor S, Scala E, Janakiraman M, Liska D, Valtorta E, Schiavo R, Buscarino M, Siravegna G, et al. Emergence of KRAS mutations and acquired resistance to anti-EGFR therapy in colorectal cancer. Nature. 2012;486:532–536.
    1. Yamada T, Iwai T, Takahashi G, Kan H, Koizumi M, Matsuda A, Shinji S, Yamagishi A, Yokoyama Y, Tatsuguchi A, et al. Utility of KRAS mutation detection using circulating cell-free DNA from patients with colorectal cancer. Cancer Sci. 2016;107:936–943.
    1. Denis JA, Lacorte JM. Detection of RAS mutations in circulating tumor cells: applications in colorectal cancer and prospects. Ann Biol Clin (Paris) 2017;75:607–618.
    1. Berger AW, Schwerdel D, Welz H, Marienfeld R, Schmidt SA, Kleger A, Ettrich TJ, Seufferlein T. Treatment monitoring in metastatic colorectal cancer patients by quantification and KRAS genotyping of circulating cell-free DNA. PLoS One. 2017;12:e0174308.
    1. Kim TW, Peeters M, Thomas A, Gibbs P, Hool K, Zhang J, Ang AL, Bach BA, Price T. Impact of emergent circulating tumor DNA RAS mutation in Panitumumab-treated Chemoresistant metastatic colorectal Cancer. Clin Cancer Res. 2018;24:5602–5609.
    1. Dumbrava EI, Call SG, Huang HJ, Stuckett AL, Madwani K, Adat A, Hong DS, Piha-Paul SA, Subbiah V, Karp DD, et al. PIK3CA mutations in plasma circulating tumor DNA predict survival and treatment outcomes in patients with advanced cancers. ESMO Open. 2021;6:100230.
    1. Hofman P, Heeke S, Alix-Panabieres C, Pantel K. Liquid biopsy in the era of immuno-oncology: is it ready for prime-time use for cancer patients? Ann Oncol. 2019;30:1448–1459.
    1. Lipson EJ, Velculescu VE, Pritchard TS, Sausen M, Pardoll DM, Topalian SL, Diaz LA., Jr Circulating tumor DNA analysis as a real-time method for monitoring tumor burden in melanoma patients undergoing treatment with immune checkpoint blockade. J Immunother Cancer. 2014;2:42.
    1. Siravegna G, Mussolin B, Buscarino M, Corti G, Cassingena A, Crisafulli G, Ponzetti A, Cremolini C, Amatu A, Lauricella C, et al. Clonal evolution and resistance to EGFR blockade in the blood of colorectal cancer patients. Nat Med. 2015;21:795–801.
    1. Riva F, Bidard FC, Houy A, Saliou A, Madic J, Rampanou A, Hego C, Milder M, Cottu P, Sablin MP, et al. Patient-specific circulating tumor DNA detection during Neoadjuvant chemotherapy in triple-negative breast Cancer. Clin Chem. 2017;63:691–699.
    1. Cabel L, Riva F, Servois V, Livartowski A, Daniel C, Rampanou A, Lantz O, Romano E, Milder M, Buecher B, et al. Circulating tumor DNA changes for early monitoring of anti-PD1 immunotherapy: a proof-of-concept study. Ann Oncol. 2017;28:1996–2001.
    1. Kitahara M, Hazama S, Tsunedomi R, Takenouchi H, Kanekiyo S, Inoue Y, Nakajima M, Tomochika S, Tokuhisa Y, Iida M, et al. Prediction of the efficacy of immunotherapy by measuring the integrity of cell-free DNA in plasma in colorectal cancer. Cancer Sci. 2016;107:1825–1829.
    1. Willis J, Lefterova MI, Artyomenko A, Kasi PM, Nakamura Y, Mody K, Catenacci DVT, Fakih M, Barbacioru C, Zhao J, et al. Validation of microsatellite instability detection using a comprehensive plasma-based genotyping panel. Clin Cancer Res. 2019;25:7035–7045.
    1. Tieng FYF, Abu N, Lee L-H, Ab Mutalib NS. Microsatellite Instability in Colorectal Cancer Liquid Biopsy-Current Updates on Its Potential in Non-Invasive Detection, Prognosis and as a Predictive Marker. Diagnostics (Basel, Switzerland). 2021;11:544.
    1. Chan TA, Yarchoan M, Jaffee E, Swanton C, Quezada SA, Stenzinger A, Peters S. Development of tumor mutation burden as an immunotherapy biomarker: utility for the oncology clinic. Ann Oncol. 2019;30:44–56.
    1. Goodman AM, Kato S, Bazhenova L, Patel SP, Frampton GM, Miller V, Stephens PJ, Daniels GA, Kurzrock R. Tumor mutational burden as an independent predictor of response to immunotherapy in diverse cancers. Mol Cancer Ther. 2017;16:2598–2608.
    1. Bardelli A, Pantel K. Liquid biopsies, what we do not know (yet) Cancer Cell. 2017;31:172–179.
    1. Zhang BO, Xu CW, Shao Y, Wang HT, Wu YF, Song YY, Li XB, Zhang Z, Wang WJ, Li LQ, Cai CL. Comparison of droplet digital PCR and conventional quantitative PCR for measuring EGFR gene mutation. Exp Ther Med. 2015;9:1383–1388.
    1. Markou A, Tzanikou E, Ladas I, Makrigiorgos GM, Lianidou E. Nuclease-assisted minor allele enrichment using overlapping probes-assisted amplification-refractory mutation system: an approach for the improvement of amplification-refractory mutation system-polymerase chain reaction specificity in liquid biopsies. Anal Chem. 2019;91:13105–13111.
    1. Lang AH, Drexel H, Geller-Rhomberg S, Stark N, Winder T, Geiger K, Muendlein A. Optimized allele-specific real-time PCR assays for the detection of common mutations in KRAS and BRAF. J Mol Diagn. 2011;13:23–28.
    1. Forshew T, Murtaza M, Parkinson C, Gale D, Tsui DW, Kaper F, Dawson SJ, Piskorz AM, Jimenez-Linan M, Bentley D, et al. Noninvasive identification and monitoring of cancer mutations by targeted deep sequencing of plasma DNA. Sci Transl Med. 2012;4:136ra168.
    1. Kinde I, Wu J, Papadopoulos N, Kinzler KW, Vogelstein B. Detection and quantification of rare mutations with massively parallel sequencing. Proc Natl Acad Sci U S A. 2011;108:9530–9535.
    1. Newman AM, Bratman SV, To J, Wynne JF, Eclov NC, Modlin LA, Liu CL, Neal JW, Wakelee HA, Merritt RE, et al. An ultrasensitive method for quantitating circulating tumor DNA with broad patient coverage. Nat Med. 2014;20:548–554.
    1. Corcoran RB, Chabner BA. Application of cell-free DNA analysis to Cancer treatment. N Engl J Med. 2018;379:1754–1765.
    1. Elazezy M, Joosse SA. Techniques of using circulating tumor DNA as a liquid biopsy component in cancer management. Comput Struct Biotechnol J. 2018;16:370–378.
    1. van der Pol Y, Mouliere F. Toward the early detection of Cancer by decoding the epigenetic and environmental fingerprints of cell-free DNA. Cancer Cell. 2019;36:350–368.
    1. Zhang H, Liu R, Yan C, Liu L, Tong Z, Jiang W, Yao M, Fang W, Chen Z. Advantage of next-generation sequencing in dynamic monitoring of circulating tumor DNA over droplet digital PCR in Cetuximab treated colorectal Cancer patients. Transl Oncol. 2019;12:426–431.
    1. Chen M, Zhao H. Next-generation sequencing in liquid biopsy: cancer screening and early detection. Hum Genomics. 2019;13:34.
    1. Ye P, Cai P, Xie J, Wei Y. The diagnostic accuracy of digital PCR, ARMS and NGS for detecting KRAS mutation in cell-free DNA of patients with colorectal cancer: a systematic review and meta-analysis. PLoS One. 2021;16:e0248775.
    1. Raposo G, Stoorvogel W. Extracellular vesicles: exosomes, microvesicles, and friends. J Cell Biol. 2013;200:373–383.
    1. Sadik N, Cruz L, Gurtner A, Rodosthenous RS, Dusoswa SA, Ziegler O, Van Solinge TS, Wei Z, Salvador-Garicano AM, Gyorgy B, et al. Extracellular RNAs: a new awareness of old perspectives. Methods Mol Biol. 2018;1740:1–15.
    1. Oliveira GP, Jr., Zigon E, Rogers G, Davodian D, Lu S, Jovanovic-Talisman T, Jones J, Tigges J, Tyagi S, Ghiran IC. Detection of Extracellular Vesicle RNA Using Molecular Beacons. iScience. 2020;23:100782.
    1. Gusachenko ON, Zenkova MA, Vlassov VV. Nucleic acids in exosomes: disease markers and intercellular communication molecules. Biochemistry (Mosc) 2013;78:1–7.
    1. Colombo M, Raposo G, Théry C. Biogenesis, secretion, and intercellular interactions of exosomes and other extracellular vesicles. Annu Rev Cell Dev Biol. 2014;30:255–289.
    1. Wang J, Yan F, Zhao Q, Zhan F, Wang R, Wang L, Zhang Y, Huang X. Circulating exosomal miR-125a-3p as a novel biomarker for early-stage colon cancer. Sci Rep. 2017;7:4150.
    1. Matsumura T, Sugimachi K, Iinuma H, Takahashi Y, Kurashige J, Sawada G, Ueda M, Uchi R, Ueo H, Takano Y, et al. Exosomal microRNA in serum is a novel biomarker of recurrence in human colorectal cancer. Br J Cancer. 2015;113:275–281.
    1. Liu X, Pan B, Sun L, Chen X, Zeng K, Hu X, Xu T, Xu M, Wang S. Circulating Exosomal miR-27a and miR-130a act as novel diagnostic and prognostic biomarkers of colorectal Cancer. Cancer Epidemiol Biomark Prev. 2018;27:746–754.
    1. Wei R, Chen L, Qin D, Guo Q, Zhu S, Li P, Min L, Zhang S. Liquid biopsy of extracellular vesicle-derived miR-193a-5p in colorectal Cancer and discovery of its tumor-suppressor functions. Front Oncol. 2020;10:1372.
    1. Kou CH, Zhou T, Han XL, Zhuang HJ, Qian HX. Downregulation of mir-23b in plasma is associated with poor prognosis in patients with colorectal cancer. Oncol Lett. 2016;12:4838–4844.
    1. Zhao YJ, Song X, Niu L, Tang Y, Song X, Xie L. Circulating Exosomal miR-150-5p and miR-99b-5p as diagnostic biomarkers for colorectal Cancer. Front Oncol. 2019;9:1129.
    1. Wang Q, Huang Z, Ni S, Xiao X, Xu Q, Wang L, Huang D, Tan C, Sheng W, Du X. Plasma miR-601 and miR-760 are novel biomarkers for the early detection of colorectal cancer. PLoS One. 2012;7:e44398.
    1. Hu HY, Yu CH, Zhang HH, Zhang SZ, Yu WY, Yang Y, Chen Q. Exosomal miR-1229 derived from colorectal cancer cells promotes angiogenesis by targeting HIPK2. Int J Biol Macromol. 2019;132:470–477.
    1. Fu F, Jiang W, Zhou L, Chen Z. Circulating Exosomal miR-17-5p and miR-92a-3p predict pathologic stage and grade of colorectal Cancer. Transl Oncol. 2018;11:221–232.
    1. Yan S, Han B, Gao S, Wang X, Wang Z, Wang F, Zhang J, Xu D, Sun B. Exosome-encapsulated microRNAs as circulating biomarkers for colorectal cancer. Oncotarget. 2017;8:60149–60158.
    1. Peng ZY, Gu RH, Yan B. Downregulation of exosome-encapsulated miR-548c-5p is associated with poor prognosis in colorectal cancer. J Cell Biochem. 2018;120:1457–1463.
    1. Sun H, Meng Q, Shi C, Yang H, Li X, Wu S, Familiari G, Relucenti M, Aschner M, Wang X, Chen R. Hypoxia-inducible Exosomes facilitate liver-tropic Premetastatic niche in colorectal Cancer. Hepatology. 2021;74:2633–2651.
    1. Tanaka S, Hosokawa M, Miyamoto T, Nakagawa A, Haruna M, Ueda K, Iwakawa S, Ogawara KI. miR-33a-5p in small extracellular vesicles as non-invasive biomarker for oxaliplatin sensitivity in human colorectal cancer cells. Biochem Biophys Rep. 2021;26:100996.
    1. Ning T, Li J, He Y, Zhang H, Wang X, Deng T, Liu R, Li H, Bai M, Fan Q, et al. Exosomal miR-208b related with oxaliplatin resistance promotes Treg expansion in colorectal cancer. Mol Ther. 2021;29:2723–2736.
    1. Han J, Sun W, Liu R, Zhou Z, Zhang H, Chen X, Ba Y. Plasma Exosomal miRNA expression profile as Oxaliplatin-based Chemoresistant biomarkers in colorectal adenocarcinoma. Front Oncol. 2020;10:1495.
    1. Bjørnetrø T, Redalen KR, Meltzer S, Thusyanthan NS, Samiappan R, Jegerschöld C, Handeland KR, Ree AH. An experimental strategy unveiling exosomal microRNAs 486-5p, 181a-5p and 30d-5p from hypoxic tumour cells as circulating indicators of high-risk rectal cancer. J Extracell Vesicles. 2019;8:1567219.
    1. Ge L, Zhou F, Nie J, Wang X, Zhao Q. Hypoxic colorectal cancer-secreted exosomes deliver miR-210-3p to normoxic tumor cells to elicit a protumoral effect. Exp Biol Med (Maywood) 2021;246:1895–1906.
    1. Hu D, Zhan Y, Zhu K, Bai M, Han J, Si Y, Zhang H, Kong D. Plasma Exosomal long non-coding RNAs serve as biomarkers for early detection of colorectal Cancer. Cell Physiol Biochem. 2018;51:2704–2715.
    1. Yu M, Song XG, Zhao YJ, Dong XH, Niu LM, Zhang ZJ, Shang XL, Tang YY, Song XR, Xie L. Circulating serum Exosomal long non-coding RNAs FOXD2-AS1, NRIR, and XLOC_009459 AS diagnostic biomarkers for colorectal Cancer. Front Oncol. 2021;11:618967.
    1. Yin H, Hu J, Ye Z, Chen S, Chen Y. Serum long non-coding RNA NNT-AS1 protected by exosome is a potential biomarkerand functions as an oncogene via the miR-496/RAP2C axis in colorectal cancer. Mol Med Rep. 2021;24:585.
    1. Ren J, Ding L, Zhang D, Shi G, Xu Q, Shen S, Wang Y, Wang T, Hou Y. Carcinoma-associated fibroblasts promote the stemness and chemoresistance of colorectal cancer by transferring exosomal lncRNA H19. Theranostics. 2018;8:3932–3948.
    1. Deng X, Ruan H, Zhang X, Xu X, Zhu Y, Peng H, Zhang X, Kong F, Guan M. Long noncoding RNA CCAL transferred from fibroblasts by exosomes promotes chemoresistance of colorectal cancer cells. Int J Cancer. 2020;146:1700–1716.
    1. Yang YN, Zhang R, Du JW, Yuan HH, Li YJ, Wei XL, Du XX, Jiang SL, Han Y. Predictive role of UCA1-containing exosomes in cetuximab-resistant colorectal cancer. Cancer Cell Int. 2018;18:164.
    1. Chen X, Liu Y, Zhang Q, Liu B, Cheng Y, Zhang Y, Sun Y, Liu J, Gen H. Exosomal long non-coding RNA HOTTIP increases resistance of colorectal Cancer cells to Mitomycin via impairing MiR-214-mediated degradation of KPNA3. Front Cell Dev Biol. 2020;8:582723.
    1. Pan B, Qin J, Liu X, He B, Wang X, Pan Y, Sun H, Xu T, Xu M, Chen X, et al. Identification of serum Exosomal hsa-circ-0004771 as a novel diagnostic biomarker of colorectal Cancer. Front Genet. 2019;10:1096.
    1. Li Y, Li C, Xu R, Wang Y, Li D, Zhang B. A novel circFMN2 promotes tumor proliferation in CRC by regulating the miR-1182/hTERT signaling pathways. Clin Sci (Lond) 2019;133:2463–2479.
    1. Yang H, Zhang H, Yang Y, Wang X, Deng T, Liu R, Ning T, Bai M, Li H, Zhu K, et al. Hypoxia induced exosomal circRNA promotes metastasis of colorectal Cancer via targeting GEF-H1/RhoA axis. Theranostics. 2020;10:8211–8226.
    1. Shang A, Gu C, Wang W, Wang X, Sun J, Zeng B, Chen C, Chang W, Ping Y, Ji P, et al. Exosomal circPACRGL promotes progression of colorectal cancer via the miR-142-3p/miR-506-3p- TGF-β1 axis. Mol Cancer. 2020;19:117.
    1. Zhao H, Chen S, Fu Q. Exosomes from CD133(+) cells carrying circ-ABCC1 mediate cell stemness and metastasis in colorectal cancer. J Cell Biochem. 2020;121:3286–3297.
    1. Xu Y, Qiu A, Peng F, Tan X, Wang J, Gong X. Exosomal transfer of circular RNA FBXW7 ameliorates the chemoresistance to oxaliplatin in colorectal cancer by sponging miR-18b-5p. Neoplasma. 2021;68:108–118.
    1. Zhao K, Cheng X, Ye Z, Li Y, Peng W, Wu Y, et al. Exosome-mediated transfer of circ_0000338 enhances 5-fluorouracil resistance in colorectal Cancer through regulating MicroRNA 217 (miR-217) and miR-485-3p. Mol Cell Biol. 2021;41(5):e00517–20.
    1. Wang X, Zhang H, Yang H, Bai M, Ning T, Deng T, Liu R, Fan Q, Zhu K, Li J, et al. Exosome-delivered circRNA promotes glycolysis to induce chemoresistance through the miR-122-PKM2 axis in colorectal cancer. Mol Oncol. 2020;14:539–555.
    1. Sun B, Li Y, Zhou Y, Ng TK, Zhao C, Gan Q, Gu X, Xiang J. Circulating exosomal CPNE3 as a diagnostic and prognostic biomarker for colorectal cancer. J Cell Physiol. 2019;234:1416–1425.
    1. Ganig N, Baenke F, Thepkaysone ML, Lin K, Rao VS, Wong FC, et al. Proteomic analyses of fibroblast- and serum-derived Exosomes identify QSOX1 as a marker for non-invasive detection of colorectal Cancer. Cancers (Basel). 2021;13(6):1351.
    1. Yun CW, Lee JH, Go G, Jeon J, Yoon S, Lee SH. Prion protein of extracellular vesicle regulates the progression of colorectal Cancer. Cancers (Basel). 2021;13(9):2144.
    1. Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004;116:281–297.
    1. Detassis S, Grasso M, Del Vescovo V, Denti MA. microRNAs make the Call in Cancer personalized medicine. Front Cell Dev Biol. 2017;5:86.
    1. Suzuki HI, Katsura A, Matsuyama H, Miyazono K. MicroRNA regulons in tumor microenvironment. Oncogene. 2015;34:3085–3094.
    1. Matsuzaki J, Ochiya T. Circulating microRNAs and extracellular vesicles as potential cancer biomarkers: a systematic review. Int J Clin Oncol. 2017;22:413–420.
    1. Yoshioka Y, Kosaka N, Konishi Y, Ohta H, Okamoto H, Sonoda H, Nonaka R, Yamamoto H, Ishii H, Mori M, et al. Ultra-sensitive liquid biopsy of circulating extracellular vesicles using ExoScreen. Nat Commun. 2014;5:3591.
    1. Alves Dos Santos K, Clemente Dos Santos IC, Santos Silva C, Gomes Ribeiro H, de Farias Domingos I, Nogueira Silbiger V. Circulating Exosomal miRNAs as Biomarkers for the Diagnosis and Prognosis of Colorectal Cancer. Int J Mol Sci. 2020;22(1):346.
    1. Maleki M, Golchin A, Javadi S, Khelghati N, Morovat P, Asemi Z, et al. Role of exosomal miRNA in chemotherapy resistance of colorectal cancer: a systematic review. Chem Biol Drug Des. 2021. Online ahead of print.
    1. Cai J, Zuo X, Chen Z, Zhang Y, Wang J, Wang J, Ye X, Zhao W. Long noncoding RNAs serve as potential diagnostic biomarkers for colorectal Cancer. J Cancer. 2019;10:611–619.
    1. Tan SK, Pastori C, Penas C, Komotar RJ, Ivan ME, Wahlestedt C, Ayad NG. Serum long noncoding RNA HOTAIR as a novel diagnostic and prognostic biomarker in glioblastoma multiforme. Mol Cancer. 2018;17:74.
    1. Oehme F, Krahl S, Gyorffy B, Muessle B, Rao V, Greif H, Ziegler N, Lin K, Thepkaysone ML, Polster H, et al. Low level of exosomal long non-coding RNA HOTTIP is a prognostic biomarker in colorectal cancer. RNA Biol. 2019;16:1339–1345.
    1. Han B, Chao J, Yao H. Circular RNA and its mechanisms in disease: from the bench to the clinic. Pharmacol Ther. 2018;187:31–44.
    1. Salzman J. Circular RNA expression: its potential regulation and function. Trends Genet. 2016;32:309–316.
    1. Barrett SP, Salzman J. Circular RNAs: analysis, expression and potential functions. Development. 2016;143:1838–1847.
    1. Dong Y, He D, Peng Z, Peng W, Shi W, Wang J, Li B, Zhang C, Duan C. Circular RNAs in cancer: an emerging key player. J Hematol Oncol. 2017;10:2.
    1. Liu S, Wu M, Peng M. Circ_0000260 regulates the development and deterioration of gastric adenocarcinoma with cisplatin resistance by Upregulating MMP11 via targeting MiR-129-5p. Cancer Manag Res. 2020;12:10505–10519.
    1. Zhong Y, Wang D, Ding Y, Tian G, Jiang B. Circular RNA circ_0032821 contributes to oxaliplatin (OXA) resistance of gastric cancer cells by regulating SOX9 via miR-515-5p. Biotechnol Lett. 2021;43:339–351.
    1. Xu X, Tao R, Sun L, Ji X. Exosome-transferred hsa_circ_0014235 promotes DDP chemoresistance and deteriorates the development of non-small cell lung cancer by mediating the miR-520a-5p/CDK4 pathway. Cancer Cell Int. 2020;20:552.
    1. Zang R, Qiu X, Song Y, Wang Y. Exosomes mediated transfer of Circ_0000337 contributes to cisplatin (CDDP) resistance of esophageal Cancer by regulating JAK2 via miR-377-3p. Front Cell Dev Biol. 2021;9:673237.
    1. Zeng Z, Zhao Y, Chen Q, Zhu S, Niu Y, Ye Z, Hu P, Chen D, Xu P, Chen J, et al. Hypoxic exosomal HIF-1α-stabilizing circZNF91 promotes chemoresistance of normoxic pancreatic cancer cells via enhancing glycolysis. Oncogene. 2021;40:5505–5517.
    1. Zhao B, Li Z, Qin C, Li T, Wang Y, Cao H, Yang X, Wang W. Mobius strip in pancreatic cancer: biogenesis, function and clinical significance of circular RNAs. Cell Mol Life Sci. 2021;78:6201–6213.
    1. Hon KW, Ab-Mutalib NS, Abdullah NMA, Jamal R, Abu N. Extracellular vesicle-derived circular RNAs confers chemoresistance in colorectal cancer. Sci Rep. 2019;9:16497.
    1. Ding C, Yi X, Wu X, Bu X, Wang D, Wu Z, Zhang G, Gu J, Kang D. Exosome-mediated transfer of circRNA CircNFIX enhances temozolomide resistance in glioma. Cancer Lett. 2020;479:1–12.
    1. Si J, Li W, Li X, Cao L, Chen Z, Jiang Z. Heparanase confers temozolomide resistance by regulation of exosome secretion and circular RNA composition in glioma. Cancer Sci. 2021;112:3491–3506.
    1. Pan Y, Lin Y, Mi C. Cisplatin-resistant osteosarcoma cell-derived exosomes confer cisplatin resistance to recipient cells in an exosomal circ_103801-dependent manner. Cell Biol Int. 2021;45:858–868.
    1. Tu C, He J, Qi L, Ren X, Zhang C, Duan Z, Yang K, Wang W, Lu Q, Li Z. Emerging landscape of circular RNAs as biomarkers and pivotal regulators in osteosarcoma. J Cell Physiol. 2020;235:9037–9058.
    1. Sandfeld-Paulsen B, Aggerholm-Pedersen N, Bæk R, Jakobsen KR, Meldgaard P, Folkersen BH, Rasmussen TR, Varming K, Jørgensen MM, Sorensen BS. Exosomal proteins as prognostic biomarkers in non-small cell lung cancer. Mol Oncol. 2016;10:1595–1602.
    1. Melo SA, Luecke LB, Kahlert C, Fernandez AF, Gammon ST, Kaye J, LeBleu VS, Mittendorf EA, Weitz J, Rahbari N, et al. Glypican-1 identifies cancer exosomes and detects early pancreatic cancer. Nature. 2015;523:177–182.
    1. Chen IH, Xue L, Hsu CC, Paez JS, Pan L, Andaluz H, Wendt MK, Iliuk AB, Zhu JK, Tao WA. Phosphoproteins in extracellular vesicles as candidate markers for breast cancer. Proc Natl Acad Sci U S A. 2017;114:3175–3180.
    1. Chen G, Huang AC, Zhang W, Zhang G, Wu M, Xu W, Yu Z, Yang J, Wang B, Sun H, et al. Exosomal PD-L1 contributes to immunosuppression and is associated with anti-PD-1 response. Nature. 2018;560:382–386.
    1. Poggio M, Hu T, Pai CC, Chu B, Belair CD, Chang A, Montabana E, Lang UE, Fu Q, Fong L, Blelloch R. Suppression of Exosomal PD-L1 induces systemic anti-tumor immunity and memory. Cell. 2019;177:414–427.e413.
    1. Pegtel DM, Gould SJ. Exosomes. Annu Rev Biochem. 2019;88:487–514.
    1. Wang W, Luo J, Wang S. Recent Progress in isolation and detection of extracellular vesicles for Cancer diagnostics. Adv Healthc Mater. 2018;7:e1800484.
    1. Li P, Kaslan M, Lee SH, Yao J, Gao Z. Progress in Exosome Isolation Techniques Theranostics. 2017;7:789–804.
    1. Vlassov AV, Magdaleno S, Setterquist R, Conrad R. Exosomes: current knowledge of their composition, biological functions, and diagnostic and therapeutic potentials. Biochim Biophys Acta. 2012;1820:940–948.
    1. Gardiner C, Di Vizio D, Sahoo S, Théry C, Witwer KW, Wauben M, Hill AF. Techniques used for the isolation and characterization of extracellular vesicles: results of a worldwide survey. J Extracell Vesicles. 2016;5:32945.
    1. Petersen KE, Manangon E, Hood JL, Wickline SA, Fernandez DP, Johnson WP, Gale BK. A review of exosome separation techniques and characterization of B16-F10 mouse melanoma exosomes with AF4-UV-MALS-DLS-TEM. Anal Bioanal Chem. 2014;406:7855–7866.
    1. Taylor DD, Shah S. Methods of isolating extracellular vesicles impact down-stream analyses of their cargoes. Methods. 2015;87:3–10.
    1. Musante L, Tataruch DE, Holthofer H. Use and isolation of urinary exosomes as biomarkers for diabetic nephropathy. Front Endocrinol (Lausanne) 2014;5:149.
    1. Popovic M, Mazzega E, Toffoletto B, de Marco A. Isolation of anti-extra-cellular vesicle single-domain antibodies by direct panning on vesicle-enriched fractions. Microb Cell Factories. 2018;17:6.
    1. Tauro BJ, Greening DW, Mathias RA, Ji H, Mathivanan S, Scott AM, Simpson RJ. Comparison of ultracentrifugation, density gradient separation, and immunoaffinity capture methods for isolating human colon cancer cell line LIM1863-derived exosomes. Methods. 2012;56:293–304.
    1. Wu M, Ouyang Y, Wang Z, Zhang R, Huang PH, Chen C, Li H, Li P, Quinn D, Dao M, et al. Isolation of exosomes from whole blood by integrating acoustics and microfluidics. Proc Natl Acad Sci U S A. 2017;114:10584–10589.
    1. Ibsen SD, Wright J, Lewis JM, Kim S, Ko SY, Ong J, Manouchehri S, Vyas A, Akers J, Chen CC, et al. Rapid isolation and detection of Exosomes and associated biomarkers from plasma. ACS Nano. 2017;11:6641–6651.
    1. Ranjan S, Zeming KK, Jureen R, Fisher D, Zhang Y. DLD pillar shape design for efficient separation of spherical and non-spherical bioparticles. Lab Chip. 2014;14:4250–4262.
    1. Liu C, Yang Y, Wu Y. Recent advances in Exosomal protein detection via liquid biopsy biosensors for Cancer screening, diagnosis, and prognosis. AAPS J. 2018;20:41.
    1. Saad MG, Beyenal H, Dong WJ. Exosomes as powerful Engines in Cancer: isolation, Characterization and Detection Techniques. Biosensors (Basel). 2021;11(12):518.
    1. Lin S, Yu Z, Chen D, Wang Z, Miao J, Li Q, Zhang D, Song J, Cui D. Progress in microfluidics-based exosome separation and detection Technologies for Diagnostic Applications. Small. 2020;16:e1903916.
    1. Xu L, Shoaie N, Jahanpeyma F, Zhao J, Azimzadeh M, Al Jamal KT. Optical, electrochemical and electrical (nano)biosensors for detection of exosomes: a comprehensive overview. Biosens Bioelectron. 2020;161:112222.
    1. Zhao Z, Ukidve A, Kim J, Mitragotri S. Targeting strategies for tissue-specific drug delivery. Cell. 2020;181:151–167.
    1. Plantureux L, Crescence L, Dignat-George F, Panicot-Dubois L, Dubois C. Effects of platelets on cancer progression. Thromb Res. 2018;164(Suppl 1):S40–s47.
    1. Peterson JE, Zurakowski D, Italiano JE, Jr, Michel LV, Connors S, Oenick M, D'Amato RJ, Klement GL, Folkman J. VEGF, PF4 and PDGF are elevated in platelets of colorectal cancer patients. Angiogenesis. 2012;15:265–273.
    1. Plantureux L, Mège D, Crescence L, Dignat-George F, Dubois C, Panicot-Dubois L. Impacts of Cancer on platelet production, Activation and Education and Mechanisms of Cancer-Associated Thrombosis. Cancers (Basel). 2018;10(11):441.
    1. Best MG, Wesseling P, Wurdinger T. Tumor-educated platelets as a noninvasive biomarker source for Cancer detection and progression monitoring. Cancer Res. 2018;78:3407–3412.
    1. Lood C, Amisten S, Gullstrand B, Jönsen A, Allhorn M, Truedsson L, Sturfelt G, Erlinge D, Bengtsson AA. Platelet transcriptional profile and protein expression in patients with systemic lupus erythematosus: up-regulation of the type I interferon system is strongly associated with vascular disease. Blood. 2010;116:1951–1957.
    1. Olsson AK, Cedervall J. The pro-inflammatory role of platelets in cancer. Platelets. 2018;29:569–573.
    1. Xue L, Xie L, Song X, Song X. Identification of potential tumor-educated platelets RNA biomarkers in non-small-cell lung cancer by integrated bioinformatical analysis. J Clin Lab Anal. 2018;32:e22450.
    1. Sheng M, Dong Z, Xie Y. Identification of tumor-educated platelet biomarkers of non-small-cell lung cancer. Onco Targets Ther. 2018;11:8143–8151.
    1. Luo CL, Xu ZG, Chen H, Ji J, Wang YH, Hu W, Wang K, Zhang WW, Yuan CH, Wang FB. LncRNAs and EGFRvIII sequestered in TEPs enable blood-based NSCLC diagnosis. Cancer Manag Res. 2018;10:1449–1459.
    1. Goswami C, Chawla S, Thakral D, Pant H, Verma P, Malik PS. Jayadeva, Gupta R, Ahuja G, Sengupta D: molecular signature comprising 11 platelet-genes enables accurate blood-based diagnosis of NSCLC. BMC Genomics. 2020;21:744.
    1. Dong X, Song X, Ding S, Yu M, Shang X, Wang K, Chang M, Xie L, Song X. Tumor-educated platelet SNORD55 as a potential biomarker for the early diagnosis of non-small cell lung cancer. Thorac Cancer. 2021;12:659–666.
    1. Waqar W, Asghar S, Manzoor S. Platelets' RNA as biomarker trove for differentiation of early-stage hepatocellular carcinoma from underlying cirrhotic nodules. PLoS One. 2021;16:e0256739.
    1. Asghar S, Waqar W, Umar M, Manzoor S. Tumor educated platelets, a promising source for early detection of hepatocellular carcinoma: liquid biopsy an alternative approach to tissue biopsy. Clin Res Hepatol Gastroenterol. 2020;44:836–844.
    1. Best MG, Wurdinger T. Tumor-educated platelets for the earlier detection of hepatocellular carcinoma. Clin Res Hepatol Gastroenterol. 2020;44:794–795.
    1. Sol N, In 't Veld S, Vancura A, Tjerkstra M, Leurs C, Rustenburg F, Schellen P, Verschueren H, Post E, Zwaan K, et al. Tumor-educated platelet RNA for the detection and (Pseudo) progression monitoring of glioblastoma. Cell Rep Med. 2020;1:100101.
    1. Campanella R, Guarnaccia L, Cordiglieri C, Trombetta E, Caroli M, Carrabba G, et al. Tumor-educated platelets and angiogenesis in glioblastoma: another brick in the wall for novel prognostic and targetable biomarkers, changing the vision from a localized tumor to a systemic pathology. Cells. 2020;9(2):294.
    1. Mendoza-Almanza G, Burciaga-Hernández L, Maldonado V, Melendez-Zajgla J, Olmos J. Role of platelets and breast cancer stem cells in metastasis. World J Stem Cells. 2020;12:1237–1254.
    1. Plantureux L, Mège D, Crescence L, Carminita E, Robert S, Cointe S, Brouilly N, Ezzedine W, Dignat-George F, Dubois C, Panicot-Dubois L. The interaction of platelets with colorectal Cancer cells inhibits tumor growth but promotes metastasis. Cancer Res. 2020;80:291–303.
    1. Tesfamariam B. Involvement of platelets in tumor cell metastasis. Pharmacol Ther. 2016;157:112–119.
    1. Yang L, Jiang Q, Li DZ, Zhou X, Yu DS, Zhong J. TIMP1 mRNA in tumor-educated platelets is diagnostic biomarker for colorectal cancer. Aging (Albany NY) 2019;11:8998–9012.
    1. Qian W, Ge XX, Wu J, Gong FR, Wu MY, Xu MD, Lian L, Wang WJ, Li W, Tao M. Prognostic evaluation of resectable colorectal cancer using platelet-associated indicators. Oncol Lett. 2019;18:571–580.
    1. Rowley JW, Weyrich AS. Coordinate expression of transcripts and proteins in platelets. Blood. 2013;121:5255–5256.
    1. Lasham A, Fitzgerald SJ, Knowlton N, Robb T, Tsai P, Black MA, Williams L, Mehta SY, Harris G, Shelling AN, et al. A predictor of early disease recurrence in patients with breast Cancer using a cell-free RNA and protein liquid biopsy. Clin Breast Cancer. 2020;20:108–116.
    1. Olmedillas-López S, García-Arranz M, García-Olmo D. Current and emerging applications of droplet digital PCR in oncology. Mol Diagn Ther. 2017;21:493–510.
    1. Herrera M, Galindo-Pumariño C, García-Barberán V, Peña C. A snapshot of the tumor microenvironment in colorectal Cancer: the liquid biopsy. Int J Mol Sci. 2019;20.
    1. Galindo-Pumariño C, Collado M, Herrera M, Peña C. Tumor microenvironment in metastatic colorectal Cancer: the arbitrator in Patients' outcome, vol. 13. Cancers (Basel). 2021.
    1. Goon PK, Lip GY, Boos CJ, Stonelake PS, Blann AD. Circulating endothelial cells, endothelial progenitor cells, and endothelial microparticles in cancer. Neoplasia. 2006;8:79–88.
    1. Bethel K, Luttgen MS, Damani S, Kolatkar A, Lamy R, Sabouri-Ghomi M, Topol S, Topol EJ, Kuhn P. Fluid phase biopsy for detection and characterization of circulating endothelial cells in myocardial infarction. Phys Biol. 2014;11:016002.
    1. Zhu Y, Zhu J, Tian X, Zhang F, Zhao L, Zhu J, Lv K, Yang N, Wang C. Circulating endothelial progenitor cells from septic patients are associated with different infectious organisms. Ann Palliat Med. 2021;10:549–559.
    1. Nizzoli ME, Merati G, Tenore A, Picone C, Consensi E, Perotti L, Ferretti VV, Sambo M, Di Sabatino A, Iotti GA, et al. Circulating endothelial cells in COVID-19. Am J Hematol. 2020;95:E187–e188.
    1. Duong HT, Erzurum SC, Asosingh K. Pro-angiogenic hematopoietic progenitor cells and endothelial colony-forming cells in pathological angiogenesis of bronchial and pulmonary circulation. Angiogenesis. 2011;14:411–422.
    1. Manzoni M, Comolli G, Torchio M, Mazzini G, Danova M. Circulating endothelial cells and their subpopulations: role as predictive biomarkers in antiangiogenic therapy for colorectal cancer. Clin Colorectal Cancer. 2015;14:11–17.
    1. Rahbari NN, Schölch S, Bork U, Kahlert C, Schneider M, Rahbari M, Büchler MW, Weitz J, Reissfelder C. Prognostic value of circulating endothelial cells in metastatic colorectal cancer. Oncotarget. 2017;8:37491–37501.
    1. Cima I, Kong SL, Sengupta D, Tan IB, Phyo WM, Lee D, Hu M, Iliescu C, Alexander I, Goh WL, et al. Tumor-derived circulating endothelial cell clusters in colorectal cancer. Sci Transl Med. 2016;8:345ra389.
    1. Ronzoni M, Manzoni M, Mariucci S, Loupakis F, Brugnatelli S, Bencardino K, Rovati B, Tinelli C, Falcone A, Villa E, Danova M. Circulating endothelial cells and endothelial progenitors as predictive markers of clinical response to bevacizumab-based first-line treatment in advanced colorectal cancer patients. Ann Oncol. 2010;21:2382–2389.
    1. Malka D, Boige V, Jacques N, Vimond N, Adenis A, Boucher E, Pierga JY, Conroy T, Chauffert B, François E, et al. Clinical value of circulating endothelial cell levels in metastatic colorectal cancer patients treated with first-line chemotherapy and bevacizumab. Ann Oncol. 2012;23:919–927.
    1. Matsusaka S, Mishima Y, Suenaga M, Terui Y, Kuniyoshi R, Mizunuma N, Hatake K. Circulating endothelial progenitors and CXCR4-positive circulating endothelial cells are predictive markers for bevacizumab. Cancer. 2011;117:4026–4032.
    1. Gootjes EC, Kraan J, Buffart TE, Bakkerus L, Zonderhuis BM, Verhoef C, et al. CD276 positive circulating endothelial cells do not predict response to systemic therapy in advanced colorectal Cancer. Cells. 2020;9(1):124.
    1. Lin PP. Aneuploid CTC and CEC. Diagnostics (Basel). 2018;8(2):26.
    1. Roselli M, Formica V, Cereda V, Jochems C, Richards J, Grenga I, Orlandi A, Ferroni P, Guadagni F, Schlom J. The association of clinical outcome and peripheral T-cell subsets in metastatic colorectal cancer patients receiving first-line FOLFIRI plus bevacizumab therapy. Oncoimmunology. 2016;5:e1188243.
    1. Bencsikova B, Budinska E, Selingerova I, Pilatova K, Fedorova L, Greplova K, Nenutil R, Valik D, Obermannova R, Sheard MA, Zdrazilova-Dubska L. Circulating T cell subsets are associated with clinical outcome of anti-VEGF-based 1st-line treatment of metastatic colorectal cancer patients: a prospective study with focus on primary tumor sidedness. BMC Cancer. 2019;19:687.
    1. Passardi A, Scarpi E, Cavanna L, Dall'Agata M, Tassinari D, Leo S, Bernardini I, Gelsomino F, Tamberi S, Brandes AA, et al. Inflammatory indexes as predictors of prognosis and bevacizumab efficacy in patients with metastatic colorectal cancer. Oncotarget. 2016;7:33210–33219.
    1. Chang J, Lin G, Ye M, Tong D, Zhao J, Zhu D, Yu Q, Zhang W, Li W. Decreased mean platelet volume predicts poor prognosis in metastatic colorectal cancer patients treated with first-line chemotherapy: results from mCRC biomarker study. BMC Cancer. 2019;19:15.
    1. Dell'Aquila E, Cremolini C, Zeppola T, Lonardi S, Bergamo F, Masi G, Stellato M, Marmorino F, Schirripa M, Urbano F, et al. Prognostic and predictive role of neutrophil/lymphocytes ratio in metastatic colorectal cancer: a retrospective analysis of the TRIBE study by GONO. Ann Oncol. 2018;29:924–930.
    1. Waas ET, Wobbes T, Ruers T, Lomme RM, Hendriks T. Circulating gelatinases and tissue inhibitor of metalloproteinase-1 in colorectal cancer metastatic liver disease. Eur J Surg Oncol. 2006;32:756–763.
    1. Nissen NI, Karsdal M, Willumsen N. Collagens and Cancer associated fibroblasts in the reactive stroma and its relation to Cancer biology. J Exp Clin Cancer Res. 2019;38:115.
    1. Heidrich I, Ackar L, Mohammadi PM, Pantel K. Liquid biopsies: potential and challenges. Int J Cancer. 2021;148:528–545.
    1. Kilgour E, Rothwell DG, Brady G, Dive C. Liquid biopsy-based biomarkers of treatment response and resistance. Cancer Cell. 2020;37:485–495.
    1. Biswas D, Ganeshalingam J, Wan JCM. The future of liquid biopsy. Lancet Oncol. 2020;21:e550.
    1. Neumann MHD, Bender S, Krahn T, Schlange T. ctDNA and CTCs in liquid biopsy - current status and where we need to Progress. Comput Struct Biotechnol J. 2018;16:190–195.
    1. Ding Y, Li W, Wang K, Xu C, Hao M, Ding L. Perspectives of the application of liquid biopsy in colorectal Cancer. Biomed Res Int. 2020;2020:6843180.
    1. Sol N, Wurdinger T. Platelet RNA signatures for the detection of cancer. Cancer Metastasis Rev. 2017;36:263–272.
    1. Best MG, Vancura A, Wurdinger T. Platelet RNA as a circulating biomarker trove for cancer diagnostics. J Thromb Haemost. 2017;15:1295–1306.

Source: PubMed

Sponsorer og samarbejdspartnere

Medicinske tilstande

Narkotikainterventioner

3
Abonner