Liquid Biopsies in Head and Neck Cancer: Current State and Future Challenges

Lingyi Kong, Andrew C Birkeland, Lingyi Kong, Andrew C Birkeland

Abstract

Head and neck cancers are the seventh most frequent malignancy worldwide, consisting of a heterogeneous group of cancers that develop in the oral cavity, pharynx, and larynx, with head and neck squamous cell carcinoma (HNSCC) being the most common pathology. Due to limitations with screening and physical examination, HNSCC often presents in advanced disease states and is thus associated with poor survival. In this setting, liquid biopsies, or obtaining patient bodily fluid samples for cancer diagnosis and prognosis, may play a dramatic role in optimizing care for HNSCC patients. In recent years, there have been dramatic advancements in investigations focused on optimizing and implementing liquid biopsies in general, and specifically for HNSCC patients. Moving forward, there remain significant challenges in liquid biopsy technological development, as well as opportunities for the development of HNSCC liquid biopsy clinical trials and treatment paradigms. In this review, we discuss the current state of liquid biopsy technologies via circulating tumor cells, circulating tumor DNA and exosomes, approaches in head and neck cancer, challenges to optimization and application of liquid biopsies for clinical study, and future prospects for this field of research as it applies to head and neck cancer.

Keywords: circulating tumor DNA; circulating tumor cells; exosomes; head and neck cancer; head and neck squamous cell carcinoma; liquid biopsy.

Conflict of interest statement

The authors declare no conflict of interest.

References

    1. Bray F., Ferlay J., Soerjomataram I., Siegel R.L., Torre L.A., Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 2018;68:394–424. doi: 10.3322/caac.21492.
    1. Siegel R.L., Miller K.D.M., Jemal A. Cancer statistics, 2018. CA Cancer J. Clin. 2018;68:7–30. doi: 10.3322/caac.21442.
    1. Mourad M., Jetmore T., Jategaonkar A.A., Moubayed S., Moshier E., Urken M.L. Epidemiological Trends of Head and Neck Cancer in the United States: A SEER Population Study. J. Oral Maxillofac. Surg. 2017;75:2562–2572. doi: 10.1016/j.joms.2017.05.008.
    1. Fitzmaurice C. Global Burden of Disease Cancer Collaboration Global, regional, and national cancer incidence, mortality, years of life lost, years lived with disability, and disability-adjusted life-years for 29 cancer groups, 2006 to 2016: A systematic analysis for the Global Burden of Disease study. J. Clin. Oncol. 2018;36:1568. doi: 10.1200/jco.2018.36.15_suppl.1568.
    1. Gillison M.L., Chaturvedi A.K., Anderson W.F., Fakhry C. Epidemiology of Human Papillomavirus–Positive Head and Neck Squamous Cell Carcinoma. J. Clin. Oncol. 2015;33:3235–3242. doi: 10.1200/JCO.2015.61.6995.
    1. Siravegna G., Marsoni S., Siena S., Bardelli A. Integrating liquid biopsies into the management of cancer. Nat. Rev. Clin. Oncol. 2017;14:531–548. doi: 10.1038/nrclinonc.2017.14.
    1. Arantes L.M.R.B., De Carvalho A.C., Melendez M.E., Carvalho A.L. Serum, plasma and saliva biomarkers for head and neck cancer. Expert Rev. Mol. Diagn. 2018;18:85–112. doi: 10.1080/14737159.2017.1404906.
    1. Cohen J.D., Javed A.A., Thoburn C., Wong F., Tie J., Gibbs P., Schmidt C.M., Yip-Schneider M.T., Allen P.J., Schattner M., et al. Combined circulating tumor DNA and protein biomarker-based liquid biopsy for the earlier detection of pancreatic cancers. Proc. Natl. Acad. Sci. USA. 2017;114:10202–10207. doi: 10.1073/pnas.1704961114.
    1. Cohen J.D., Li L., Wang Y., Thoburn C., Afsari B., Danilova L., Douville C., Javed A.A., Wong F., Mattox A., et al. Detection and localization of surgically resectable cancers with a multi-analyte blood test. Science. 2018;359:926–930. doi: 10.1126/science.aar3247.
    1. Russano M., Napolitano A., Ribelli G., Iuliani M., Simonetti S., Citarella F., Pantano F., Dell’Aquila E., Anesi C., Silvestris N., et al. Correction to: Liquid biopsy and tumor heterogeneity in metastatic solid tumors: The potentiality of blood samples. J. Exp. Clin. Cancer Res. 2020;39:120. doi: 10.1186/s13046-020-01615-w.
    1. Guthrie G.J., Charles K.A., Roxburgh C.S., Horgan P.G., McMillan D.C., Clarke S.J. The systemic inflammation-based neutrophil–lymphocyte ratio: Experience in patients with cancer. Crit. Rev. Oncol. 2013;88:218–230. doi: 10.1016/j.critrevonc.2013.03.010.
    1. Shanmugam A., Hariharan A.K., Hasina R., Nair J.R., Katragadda S., Irusappan S., Ravichandran A., Veeramachaneni V., Bettadapura R., Bhati M., et al. Ultrasensitive detection of tumor-specific mutations in saliva of patients with oral cavity squamous cell carcinoma. Cancer. 2021 doi: 10.1002/cncr.33393.
    1. Pantel K., Brakenhoff R.H., Brandt B. Detection, clinical relevance and specific biological properties of disseminating tumour cells. Nat. Rev. Cancer. 2008;8:329–340. doi: 10.1038/nrc2375.
    1. Liu H.E., Triboulet M., Zia A., Vuppalapaty M., Kidess-Sigal E., Coller J., Natu V.S., Shokoohi V., Che J., Renier C., et al. Workflow optimization of whole genome amplification and targeted panel sequencing for CTC mutation detection. NPJ Genom. Med. 2017;2:34. doi: 10.1038/s41525-017-0034-3.
    1. Luo A., Zhou X., Shi X., Zhao Y., Men Y., Chang X., Chen H., Ding F., Li Y., Su D., et al. Exosome-derived miR-339-5p mediates radiosensitivity by targeting Cdc25A in locally advanced esophageal squamous cell carcinoma. Oncogene. 2019;38:4990–5006. doi: 10.1038/s41388-019-0771-0.
    1. Alix-Panabières C., Pantel K. Challenges in circulating tumour cell research. Nat. Rev. Cancer. 2014;14:623–631. doi: 10.1038/nrc3820.
    1. de Wit S., van Dalum G., Terstappen L.W. Detection of circulating tumor cells. Scientifica. 2014;2014:819362. doi: 10.1155/2014/819362.
    1. Zeisberg M., Neilson E.G. Biomarkers for epithelial-mesenchymal transitions. J. Clin. Investig. 2009;119:1429–1437. doi: 10.1172/JCI36183.
    1. Lu Y., Liang H., Yu T., Xie J., Chen S., Dong H., Sinko P.J., Lian S., Xu J., Wang J., et al. Isolation and characterization of living circulating tumor cells in patients by immunomagnetic negative enrichment coupled with flow cytometry. Cancer. 2015;121:3036–3045. doi: 10.1002/cncr.29444.
    1. Shen Z., Wu A., Chen X. Current detection technologies for circulating tumor cells. Chem. Soc. Rev. 2017;46:2038–2056. doi: 10.1039/C6CS00803H.
    1. Onidani K., Shoji H., Kakizaki T., Yoshimoto S., Okaya S., Miura N., Sekikawa S., Furuta K., Lim C.T., Shibahara T., et al. Monitoring of cancer patients via next-generation sequencing of patient-derived circulating tumor cells and tumor DNA. Cancer Sci. 2019;110:2590–2599. doi: 10.1111/cas.14092.
    1. Liao C.-J., Hsieh C.-H., Hung F.-C., Wang H.-M., Chou W.-P., Wu M.-H. The Integration of a Three-Dimensional Spheroid Cell Culture Operation in a Circulating Tumor Cell (CTC) Isolation and Purification Process: A Preliminary Study of the Clinical Significance and Prognostic Role of the CTCs Isolated from the Blood Samples of Head and Neck Cancer Patients. Cancers. 2019;11:783. doi: 10.3390/cancers11060783.
    1. Jatana K.R., Balasubramanian P., Lang J.C., Yang L., Jatana C.A., White E., Agrawal A., Ozer E., Schuller D.E., Chalmers J.J., et al. Significance of circulating tumor cells in patients with squamous cell carcinoma of the head and neck: Initial results. Arch. Otolaryngol. Head Neck Surg. 2010;136:1274–1279. doi: 10.1001/archoto.2010.223.
    1. Tinhofer I., Konschak R., Stromberger C., Raguse J.-D., Dreyer J.H., Jöhrens K., Keilholz U., Budach V. Detection of circulating tumor cells for prediction of recurrence after adjuvant chemoradiation in locally advanced squamous cell carcinoma of the head and neck. Ann. Oncol. 2014;25:2042–2047. doi: 10.1093/annonc/mdu271.
    1. Kulasinghe A., Kapeleris J., Kimberley R., Mattarollo S.R., Thompson E.W., Thiery J.P., O’Byrne K., Punyadeera C. The prognostic significance of circulating tumor cells in head and neck and non-small-cell lung cancer. Cancer Med. 2018;7:5910–5919. doi: 10.1002/cam4.1832.
    1. Inhestern J., Oertel K., Stemmann V., Schmalenberg H., Dietz A., Rotter N., Veit J., Görner M., Sudhoff H., Junghanß C., et al. Prognostic Role of Circulating Tumor Cells during Induction Chemotherapy Followed by Curative Surgery Combined with Postoperative Radiotherapy in Patients with Locally Advanced Oral and Oropharyngeal Squamous Cell Cancer. PLoS ONE. 2015;10:e0132901. doi: 10.1371/journal.pone.0132901.
    1. Wang H., Wu M., Chang P., Lin H., Liao C., Wu S., Hung T., Lin C., Chang T., Tzu-Tsen Y., et al. The change in circulating tumor cells before and during concurrent chemoradiotherapy is associated with survival in patients with locally advanced head and neck cancer. Head Neck. 2019;41:2676–2687. doi: 10.1002/hed.25744.
    1. Hristozova T., Konschak R., Stromberger C., Fusi A., Liu Z., Weichert W., Stenzinger A., Budach V., Keilholz U., Tinhofer I. The presence of circulating tumor cells (CTCs) correlates with lymph node metastasis in nonresectable squamous cell carcinoma of the head and neck region (SCCHN) Ann. Oncol. 2011;22:1878–1885. doi: 10.1093/annonc/mdr130.
    1. Strati A., Koutsodontis G., Papaxoinis G., Angelidis I., Zavridou M., Economopoulou P., Kotsantis I., Avgeris M., Mazel M., Perisanidis C., et al. Prognostic significance of PD-L1 expression on circulating tumor cells in patients with head and neck squamous cell carcinoma. Ann. Oncol. Off. J. Eur. Soc. Med. Oncol. 2017;28:1923–1933. doi: 10.1093/annonc/mdx206.
    1. Sharma P., Allison J.P. The future of immune checkpoint therapy. Science. 2015;348:56–61. doi: 10.1126/science.aaa8172.
    1. Oliveira-Costa J.P., De Carvalho A.F., Da Silveira D.G.G., Amaya P., Wu Y., Park K.-J.J., Gigliola M.P., Lustberg M., Buim M.E.C., Ferreira E.N., et al. Gene expression patterns through oral squamous cell carcinoma development: PD-L1 expression in primary tumor and circulating tumor cells. Oncotarget. 2015;6:20902–20920. doi: 10.18632/oncotarget.3939.
    1. Kulasinghe A., Kenny L., Punyadeera C. Circulating tumour cell PD-L1 test for head and neck cancers. Oral Oncol. 2017;75:6–7. doi: 10.1016/j.oraloncology.2017.10.011.
    1. Chikamatsu K., Tada H., Takahashi H., Kuwabara-Yokobori Y., Ishii H., Ida S., Shino M. Expression of immune-regulatory molecules in circulating tumor cells derived from patients with head and neck squamous cell carcinoma. Oral Oncol. 2019;89:34–39. doi: 10.1016/j.oraloncology.2018.12.002.
    1. Thierry A.R., El Messaoudi S., Gahan P.B., Anker P., Stroun M. Origins, structures, and functions of circulating DNA in oncology. Cancer Metastasis Rev. 2016;35:347–376. doi: 10.1007/s10555-016-9629-x.
    1. Jahr S., Hentze H., Englisch S., Hardt D., Fackelmayer F.O., Hesch R.D., Knippers R. DNA fragments in the blood plasma of cancer patients: Quantitations and evidence for their origin from apoptotic and necrotic cells. Cancer Res. 2001;61:1659–1665.
    1. Diehl F., Schmidt K., Choti M.A., Romans K.E., Goodman S.N., Li M., Thornton K., Agrawal N., Sokoll L.J., Szabo S.A., et al. Circulating mutant DNA to assess tumor dynamics. Nat. Med. 2008;14:985–990. doi: 10.1038/nm.1789.
    1. Holdhoff M., Schmidt K., Donehower R., Diaz L.A. Analysis of Circulating Tumor DNA to Confirm Somatic KRAS Mutations. J. Natl. Cancer Inst. 2009;101:1284–1285. doi: 10.1093/jnci/djp240.
    1. Han X., Wang J., Sun Y. Circulating Tumor DNA as Biomarkers for Cancer Detection. Genom. Proteom. Bioinform. 2017;15:59–72. doi: 10.1016/j.gpb.2016.12.004.
    1. Liu Q., Sommer S.S. Pyrophosphorolysis-Activated Polymerization (PAP): Application to Allele-Specific Amplification. Biotechniques. 2000;29:1072–1083. doi: 10.2144/00295rr03.
    1. Diaz L.A., Bardelli A. Liquid Biopsies: Genotyping Circulating Tumor DNA. J. Clin. Oncol. 2014;32:579–586. doi: 10.1200/JCO.2012.45.2011.
    1. Leary R.J., Sausen M., Kinde I., Papadopoulos N., Carpten J.D., Craig D., O’Shaughnessy J., Kinzler K.W., Parmigiani G., Vogelstein B., et al. Detection of Chromosomal Alterations in the Circulation of Cancer Patients with Whole-Genome Sequencing. Sci. Transl. Med. 2012;4:162ra154. doi: 10.1126/scitranslmed.3004742.
    1. van Ginkel J.H., Huibers M.M., van Es R.J., de Bree R., Willems S.M. Droplet digital PCR for detection and quantification of circulating tumor DNA in plasma of head and neck cancer patients. BMC Cancer. 2017;17:428. doi: 10.1186/s12885-017-3424-0.
    1. Mes S.W., Brink A., Sistermans E.A., Straver R., Oudejans C.B., Poell J.B., Leemans C.R., Brakenhoff R.H. Comprehensive multiparameter genetic analysis improves circulating tumor DNA detection in head and neck cancer patients. Oral Oncol. 2020;109:104852. doi: 10.1016/j.oraloncology.2020.104852.
    1. Wang Y., Springer S., Mulvey C.L., Silliman N., Schaefer J., Sausen M., James N., Rettig E.M., Guo T., Pickering C.R., et al. Detection of somatic mutations and HPV in the saliva and plasma of patients with head and neck squamous cell carcinomas. Sci. Transl. Med. 2015;7:293ra104. doi: 10.1126/scitranslmed.aaa8507.
    1. Schwaederle M., Chattopadhyay R., Kato S., Fanta P.T., Banks K.C., Choi I.S., Piccioni D.E., Ikeda S., Talasaz A., Lanman R.B., et al. Genomic Alterations in Circulating Tumor DNA from Diverse Cancer Patients Identified by Next-Generation Sequencing. Cancer Res. 2017;77:5419–5427. doi: 10.1158/0008-5472.CAN-17-0885.
    1. Palmirotta R., Lovero D., Cafforio P., Felici C., Mannavola F., Pellè E., Quaresmini D., Tucci M., Silvestris F. Liquid biopsy of cancer: A multimodal diagnostic tool in clinical oncology. Ther. Adv. Med. Oncol. 2018;10 doi: 10.1177/1758835918794630.
    1. Mazurek A.M., Rutkowski T., Fiszer-Kierzkowska A., Małusecka E., Składowski K. Assessment of the total cfDNA and HPV16/18 detection in plasma samples of head and neck squamous cell carcinoma patients. Oral Oncol. 2016;54:36–41. doi: 10.1016/j.oraloncology.2015.12.002.
    1. Bettegowda C., Sausen M., Leary R.J., Kinde I., Wang Y., Agrawal N., Bartlett B.R., Wang H., Luber B., Alani R.M., et al. Detection of Circulating Tumor DNA in Early- and Late-Stage Human Malignancies. Sci. Transl. Med. 2014;6:224ra24. doi: 10.1126/scitranslmed.3007094.
    1. Ahn S.M., Chan J.Y.K., Zhang Z., Wang H., Khan Z., Bishop J.A., Westra W., Koch W.M., Califano J.A. Saliva and Plasma Quantitative Polymerase Chain Reaction–Based Detection and Surveillance of Human Papillomavirus–Related Head and Neck Cancer. JAMA Otolaryngol. Neck Surg. 2014;140:846–854. doi: 10.1001/jamaoto.2014.1338.
    1. Chan K.A., Woo J.K., King A., Zee B.C., Lam W.J., Chan S.L., Chu S.W., Mak C., Tse I.O., Leung S.Y., et al. Analysis of Plasma Epstein–Barr Virus DNA to Screen for Nasopharyngeal Cancer. N. Engl. J. Med. 2017;377:513–522. doi: 10.1056/NEJMoa1701717.
    1. Egyud M., Sridhar P., Devaiah A., Yamada E., Saunders S., Ståhlberg A., Filges S., Krzyzanowski P.M., Kalatskaya I., Jiao W., et al. Plasma circulating tumor DNA as a potential tool for disease monitoring in head and neck cancer. Head Neck. 2019;41:1351–1358. doi: 10.1002/hed.25563.
    1. Chera B.S., Kumar S., Shen C., Amdur R., Dagan R., Green R., Goldman E., Weiss J., Grilley-Olson J., Patel S., et al. Plasma Circulating Tumor HPV DNA for the Surveillance of Cancer Recurrence in HPV-Associated Oropharyngeal Cancer. J. Clin. Oncol. Off. J. Am. Soc. Clin. Oncol. 2020;38:1050–1058. doi: 10.1200/JCO.19.02444.
    1. Dawson S.-J., Tsui D.W., Murtaza M., Biggs H., Rueda O.M., Chin S.-F., Dunning M.J., Gale D., Forshew T., Mahler-Araujo B., et al. Analysis of Circulating Tumor DNA to Monitor Metastatic Breast Cancer. N. Engl. J. Med. 2013;368:1199–1209. doi: 10.1056/NEJMoa1213261.
    1. De Maio G. Circulating and stool nucleic acid analysis for colorectal cancer diagnosis. World J. Gastroenterol. 2014;20:957–967. doi: 10.3748/wjg.v20.i4.957.
    1. Hamana K., Uzawa K., Ogawara K., Shiiba M., Bukawa H., Yokoe H., Tanzawa H. Monitoring of circulating tumour-associated DNA as a prognostic tool for oral squamous cell carcinoma. Br. J. Cancer. 2005;92:2181–2184. doi: 10.1038/sj.bjc.6602635.
    1. van Ginkel J.H., Huibers M.M., Noorlag R., de Bree R., van Es R.J., Willems S.M. Liquid biopsy: A future tool for posttreatment surveillance in head and neck cancer? Pathobiology. 2017;84:115–120. doi: 10.1159/000452861.
    1. Rutkowski T.W., Mazurek A.M., Śnietura M., Hejduk B., Jędrzejewska M., Bobek-Billewicz B., D’Amico A., Pigłowski W., Wygoda A., Składowski K., et al. Circulating HPV16 DNA may complement imaging assessment of early treatment efficacy in patients with HPV-positive oropharyngeal cancer. J. Transl. Med. 2020;18:1–10. doi: 10.1186/s12967-020-02330-y.
    1. Tanaka H., Takemoto N., Horie M., Takai E., Fukusumi T., Suzuki M., Eguchi H., Komukai S., Tatsumi M., Isohashi F., et al. Circulating tumor HPV DNA complements PET-CT in guiding management after radiotherapy in HPV -related squamous cell carcinoma of the head and neck. Int. J. Cancer. 2021;148:995–1005. doi: 10.1002/ijc.33287.
    1. Thakur B.K., Zhang H., Becker A., Matei I., Huang Y., Costa-Silva B., Zheng Y., Hoshino A., Brazier H., Xiang J., et al. Double-stranded DNA in exosomes: A novel biomarker in cancer detection. Cell Res. 2014;24:766–769. doi: 10.1038/cr.2014.44.
    1. Milane L., Singh A., Mattheolabakis G., Suresh M., Amiji M.M. Exosome mediated communication within the tumor microenvironment. J. Control. Release. 2015;219:278–294. doi: 10.1016/j.jconrel.2015.06.029.
    1. Lee Y., El Andaloussi S., Wood M.J. Exosomes and microvesicles: Extracellular vesicles for genetic information transfer and gene therapy. Hum. Mol. Genet. 2012;21:R125–R134. doi: 10.1093/hmg/dds317.
    1. Harding C.V., Heuser J.E., Stahl P.D. Exosomes: Looking back three decades and into the future. J. Cell Biol. 2013;200:367–371. doi: 10.1083/jcb.201212113.
    1. Li P., Kaslan M., Lee S.H., Yao J., Gao Z. Progress in Exosome Isolation Techniques. Theranostics. 2017;7:789–804. doi: 10.7150/thno.18133.
    1. Hong C.-S., Funk S., Muller L., Boyiadzis M., Whiteside T.L. Isolation of biologically active and morphologically intact exosomes from plasma of patients with cancer. J. Extracell. Vesicles. 2016;5:29289. doi: 10.3402/jev.v5.29289.
    1. D’Souza-Schorey C., Clancy J.W. Tumor-derived microvesicles: Shedding light on novel microenvironment modulators and prospective cancer biomarkers. Genes Dev. 2012;26:1287–1299. doi: 10.1101/gad.192351.112.
    1. Ludwig S., Floros T., Theodoraki M.-N., Hong C.-S., Jackson E.K., Lang S., Whiteside T.L. Suppression of Lymphocyte Functions by Plasma Exosomes Correlates with Disease Activity in Patients with Head and Neck Cancer. Clin. Cancer Res. 2017;23:4843–4854. doi: 10.1158/1078-0432.CCR-16-2819.
    1. Theodoraki M.-N., Yerneni S.S., Hoffmann T.K., Gooding W.E., Whiteside T.L. Clinical Significance of PD-L1+ Exosomes in Plasma of Head and Neck Cancer Patients. Clin. Cancer Res. 2018;24:896–905. doi: 10.1158/1078-0432.CCR-17-2664.
    1. Wang J., Zhou Y., Lu J., Sun Y., Xiao H., Liu M., Tian L. Combined detection of serum exosomal miR-21 and HOTAIR as diagnostic and prognostic biomarkers for laryngeal squamous cell carcinoma. Med Oncol. 2014;31:1–8. doi: 10.1007/s12032-014-0148-8.
    1. Theodoraki M.-N., Yerneni S.S., Brunner C., Theodorakis J., Hoffmann T.K., Whiteside T.L. Plasma-derived Exosomes Reverse Epithelial-to-Mesenchymal Transition after Photodynamic Therapy of Patients with Head and Neck Cancer. Oncoscience. 2018;5:75–87. doi: 10.18632/oncoscience.410.
    1. Theodoraki M.-N., Yerneni S., Gooding W.E., Ohr J., Clump D.A., Bauman J.E., Ferris R.L., Whiteside T.L. Circulating exosomes measure responses to therapy in head and neck cancer patients treated with cetuximab, ipilimumab, and IMRT. OncoImmunology. 2019;8:e1593805. doi: 10.1080/2162402X.2019.1593805.
    1. Ferris R.L. Immunology and Immunotherapy of Head and Neck Cancer. J. Clin. Oncol. 2015;33:3293–3304. doi: 10.1200/JCO.2015.61.1509.
    1. Hammond S.M., Bernstein E., Beach D., Hannon G.J. An RNA-directed nuclease mediates post-transcriptional gene silencing in Drosophila cells. Nat. Cell Biol. 2000;404:293–296. doi: 10.1038/35005107.
    1. Langevin S., Kuhnell D., Parry T., Biesiada J., Huang S., Wise-Draper T., Casper K., Zhang X., Medvedovic M., Kasper S. Comprehensive microRNA-sequencing of exosomes derived from head and neck carcinoma cells in vitro reveals common secretion profiles and potential utility as salivary biomarkers. Oncotarget. 2017;8:82459. doi: 10.18632/oncotarget.19614.
    1. Li L., Li C., Wang S., Wang Z., Jiang J., Wang W., Li X., Chen J., Liu K., Li C., et al. Exosomes Derived from Hypoxic Oral Squamous Cell Carcinoma Cells Deliver miR-21 to Normoxic Cells to Elicit a Prometastatic Phenotype. Cancer Res. 2016;76:1770–1780. doi: 10.1158/0008-5472.CAN-15-1625.
    1. Tanaka Y., Kamohara H., Kinoshita K., Kurashige J., Ishimoto T., Iwatsuki M., Watanabe M., Baba H. Clinical impact of serum exosomal microRNA-21 as a clinical biomarker in human esophageal squamous cell carcinoma. Cancer. 2012;119:1159–1167. doi: 10.1002/cncr.27895.
    1. Mitchell P.S., Parkin R.K., Kroh E.M., Fritz B.R., Wyman S.K., Pogosova-Agadjanyan E.L., Peterson A., Noteboom J., O’Briant K.C., Allen A., et al. Circulating microRNAs as stable blood-based markers for cancer detection. Proc. Natl. Acad. Sci. USA. 2008;105:10513–10518. doi: 10.1073/pnas.0804549105.
    1. Lu Y.C., Chang J.T.C., Huang Y.C., Huang C.C., Chen W.H., Lee L.Y., Huang B.S., Chen Y.J., Li H.F., Cheng A.J. Combined determination of circulating miR-196a and miR-196b levels produces high sensitivity and specificity for early detection of oral cancer. Clin. Biochem. 2015;48:115–121. doi: 10.1016/j.clinbiochem.2014.11.020.
    1. Liu C.J., Kao S.Y., Tu H.F., Tsai M.M., Chang K.W., Lin S.C. Increase of microRNA miR-31 level in plasma could be a potential marker of oral cancer. Oral Diseases. 2010;16:360–364. doi: 10.1111/j.1601-0825.2009.01646.x.
    1. Fayda M., Isin M., Tambas M., Guveli M., Meral R., Altun M., Sahin D., Ozkan G., Sanli Y., Gezer U. Do circulating long non-coding RNAs (lncRNAs)(LincRNA-p21, GAS 5, HOTAIR) predict the treatment response in patients with head and neck cancer treated with chemoradiotherapy? Tumor Biol. 2016;37:3969–3978. doi: 10.1007/s13277-015-4189-1.
    1. Shahid N., Iqbal A., Siddiqui A.J., Shoaib M., Musharraf S.G. Plasma metabolite profiling and chemometric analyses of tobacco snuff dippers and patients with oral cancer: Relationship between metabolic signatures. Head Neck. 2018;41:291–300. doi: 10.1002/hed.25511.
    1. Yin M.-Z., Tan S., Li X., Hou Y., Cao G., Li K., Kou J., Lou G. Identification of phosphatidylcholine and lysophosphatidylcholine as novel biomarkers for cervical cancers in a prospective cohort study. Tumor Biol. 2015;37:5485–5492. doi: 10.1007/s13277-015-4164-x.
    1. Xu J., Chen Y., Zhang R., Song Y., Cao J., Bi N., Wang J., He J., Bai J., Abliz Z., et al. Global and targeted metabolomics of esophageal squamous cell carcinoma discovers potential diagnostic and therapeutic biomarkers. Mol. Cell. Proteom. 2013;12:1306–1318. doi: 10.1074/mcp.M112.022830.
    1. Wojakowska A., Zebrowska A., Skowronek A., Rutkowski T., Polanski K., Widlak P., Marczak L., Pietrowska M. Metabolic Profiles of Whole Serum and Serum-Derived Exosomes Are Different in Head and Neck Cancer Patients Treated by Radiotherapy. J. Pers. Med. 2020;10:229. doi: 10.3390/jpm10040229.
    1. Best M.G., Sol N., Kooi I.E., Tannous J., Westerman B.A., 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. doi: 10.1016/j.ccell.2015.09.018.
    1. Verlingue L., Alt M., Kamal M., Sablin M.-P., Zoubir M., Bousetta N., Pierga J.-Y., Servant N., Paoletti X., Le Tourneau C. Challenges for the implementation of high-throughput testing and liquid biopsies in personalized medicine cancer trials. Pers. Med. 2014;11:545–558. doi: 10.2217/pme.14.30.
    1. Alix-Panabières C., Pantel K. Clinical Applications of Circulating Tumor Cells and Circulating Tumor DNA as Liquid Biopsy. Cancer Discov. 2016;6:479–491. doi: 10.1158/-15-1483.
    1. Chae Y.K., Oh M.S. Detection of Minimal Residual Disease Using ctDNA in Lung Cancer: Current Evidence and Future Directions. J. Thorac. Oncol. 2019;14:16–24. doi: 10.1016/j.jtho.2018.09.022.

Source: PubMed

3
订阅