microRNAs expression profile related with response to preoperative radiochemotherapy in patients with locally advanced gastric cancer

Xiaowen Liu, Hong Cai, Weiqi Sheng, Hua Huang, Ziwen Long, Yanong Wang, Xiaowen Liu, Hong Cai, Weiqi Sheng, Hua Huang, Ziwen Long, Yanong Wang

Abstract

Background: It is urgent to find some biochemical markers for predicting the radiochemotherapy sensitivity. microRNAs have a huge potential as a predictive biomarker in gastric cancer. The current study aims to identify the microRNAs related to the radiochemotherapy sensitivity in gastric cancer.

Methods: From April 2012 to August 2014, 40 patients with locally advanced gastric cancer were included into the clinical trial in the Fudan University Shanghai Cancer Center. The lesion specimens of 15 patients were obtained by gastroendoscopy before treatment, and the RNA was extracted. microRNAs array was used to identify the microRNAs with different expression level between sensitive group and non-sensitive group. The microRNAs identified in the array were further confirmed by TaqMan Real-time PCR.

Results: 2006 microRNAs were identified by microRNA array, including 302 highly expressed microRNAs and 1704 lowly expressed microRNAs between non-sensitive group and sensitive group. According to the statistical significance (p < 0.05) and expression level (more than twofold or less than 0.5 times), 9 microRNAs were identified. Finally, we chose 6 microRNAs like miR-16-2-3p, miR-340-5p, miR-338-3p, miR-142-3p, miR-142-5p and miR-582-5p to determine the sensitive group and non-sensitive group. TaqMan Real-time PCR confirmed the results of microRNA array.

Conclusions: microRNA array can be used to select the microRNAs associated with radiochemotherapy sensitivity in gastric cancer. miR-338-3p and miR-142-3p may be promising predictive biomarkers for such patients.

Trial registration: Trial Registration number: NCT03013010 . Name of registry: Phase II Study of Neoadjuvant Chemotherapy Wtih S1 + Oxaliplatin (SOX) Regimen Followed by Chemoradiation Concurrent With S-1 in Patients With Potentially Resectable Gastric Carcinoma. Date registered: December 31, 2013. The trial was prospectively registered.

Keywords: Gastric cancer; Preoperative radiochemotherapy; Response; microRNAs expression.

Conflict of interest statement

Ethics approval and consent to participate

The study was approved by the Ethics Committee of the Fudan University Shanghai Cancer Center. All patients provided written informed consent.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Hierarchical clustering analysis for the selected differentially expressed microRNAs. The horizontal axis represents the serum samples from gastric cancer patient with radiochemotherapy sensitive (group 2) (RTH, LGS, SQ, CH, CYC, WYF, CGQ, CYH, ZSQ and GYD) and non-sensitive group (NC) controls (group 1) (ZZX, XJY, WJS, SXY and CMX). The microRNA names are shown on the right vertical axis. Colored bars indicate the range of fold changes
Fig. 2
Fig. 2
Validation of selected microRNAs by qRT-PCR. miR-12-3p, miR-142-5p, miR-338-3p, miR-340-5p, miR-582-5p and miR-16-2-3p were measured in 5 non-sensitive and 10 sensitive gastric cancer patient samples
Fig. 3
Fig. 3
Receiver operating characteristic curve analysis for radiochemotherapy sensitive diagnosis. a miR-1338-3p, (b) miR-142-3p; AUC: area under the curve. ROC curve analysis was used by Medcalc

References

    1. Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin. 2015;65:87–108. doi: 10.3322/caac.21262.
    1. Wanebo HJ, Kennedy BJ, Chmiel J, et al. Cancer of the stomach: a patient care study by the American College of Surgeons. Ann Surg. 1993;218:583–592. doi: 10.1097/00000658-199321850-00002.
    1. Cunningham D, Allum WH, Stenning SP, Thompson JN, Van de velde CJ, Nicolson M, Scarffe JH, Lofts FJ, Falk SJ, Iveson TJ, Smith DB, Langley RE, Verma M, Weeden S, Chua YJ, MAGIC Trial Participants Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med. 2006;355:11–20. doi: 10.1056/NEJMoa055531.
    1. Ito S, Sano T, Mizusawa J, Takahari D, Katayama H, Katai H, Kawashima Y, Kinoshita T, Terashima M, Nashimoto A, Nakamori M, Onaya H, Sasako M. A phase II study of preoperative chemotherapy with docetaxel, cisplatin, and S-1 followed by gastrectomy with D2 plus Para-aortic lymph node dissection for gastric cancer with extensive lymph node metastasis: JCOG 1002. Gastric Cancer. 2017;20:322–331. doi: 10.1007/s10120-016-0619-z.
    1. Tsuburaya A, Mizusawa J, Tanaka Y, Fukushima N, Nashimoto A, Sasako M, Stomach Cancer Study Group of the Japan Clinical Oncology Group Neoadjuvant chemotherapy with S-1 and cisplatin followed by D2 gastrectomy with Para-aortic lymph node dissection for gastric cancer with extensive lymph node metastasis. Br J Surg. 2014;101:653–660. doi: 10.1002/bjs.9484.
    1. Ajani JA, Mansfield PF, Crane CH, Wu TT, Lunagomez S, Lynch PM, Janjan N, Feig B, Faust J, Yao JC, Nivers R, Morris J, Pisters PW. Paclitaxel-based chemoradiotherapy in localized gastric carcinoma: degree of pathologic response and not clinical parameters dictated patients outcome. J Clin Oncol. 2005;23:1237–1244. doi: 10.1200/JCO.2005.01.305.
    1. Ajani JA, Winter K, Okawara GS, Donohue JH, Pisters PW, Crane CH, Greskovich JF, Anne PR, Bradley JD, Willett C, Rich TA. Phase II trial of preoperative chemoradiation in patients with localized gastric adenocarcinoma (RTOG 9904): quality of combined modality therapy and pathologic response. J Clin Oncol. 2006;24:3953–3958. doi: 10.1200/JCO.2006.06.4840.
    1. Stahl M, Walz MK, Stuschke M, Lehmann N, Meyer HJ, Riera-Knorrenschild J, Langer P, Engenhart-Cabillic R, Bitzer M, Konigsrainer A, Budach W, Wike H. Phase III comparison of preoperative chemotherapy compared with chemoradiotherapy in patients with locally advanced adenocarcinoma of the esophagogastric junction. J Clin Oncol. 2009;27:851–856. doi: 10.1200/JCO.2008.17.0506.
    1. Pera M, Gallego R, Montagut C, Martin-Richard M, Lglesias M, Conill C, Reig A, Balague C, Petriz L, Momblan D, Bellmunt J, Maurel J. Phase II trial of preoperative chemoradiotherapy with oxaliplatin, cisplatin, and 5-FU in locally advanced esophageal and gastric cancer. Ann Oncol. 2012;23:664–670. doi: 10.1093/annonc/mdr291.
    1. Song S, Ajani JA. The role of microRNAs in cancers of the upper gastrointestinal tract. Nat Rev Gastroenterol Hepatol. 2013;10:109–118. doi: 10.1038/nrgastro.2012.210.
    1. Ishimoto T, Baba H, Izumi D, Sugihara H, Kurashige J, Iwatsuki M, Tan P. Current perspectives toward the identification of key players in gastric cancer microRNA dysregulation. Int J Cancer. 2016;138:1337–1349. doi: 10.1002/ijc.29627.
    1. Kaller M, Hermeking H. Interplay between transcription factors and MicroRNAs regulating epithelial-mesenchymal transitions in colorectal Cancer. Adv Exp Med Biol. 2016;937:71–92. doi: 10.1007/978-3-319-42059-2_4.
    1. Liu Y, Gao S, Chen X, Liu M, Mao C, Fang X. Overexpression of miR-203 sensitizes paclitaxel (Taxol)-resistant colorectal cancer cells through targeting the salt-inducible kinase 2 (SIK2) Tumour Biol. 2016;37:12231–12239. doi: 10.1007/s13277-016-5066-2.
    1. Long HC, Gao X, Lei CJ, Zhu B, Li L, Zeng C, Huang JB, Feng JR. miR-542-3p inhibits the growth and invasion of colorectal cancer cells through targeted regulation of cortactin. Int J Mol Med. 2016;37:1112–1118. doi: 10.3892/ijmm.2016.2505.
    1. Sayagués JM, Corchete LA, Gutiérrez ML, Sarasquete ME, Del Mar Abad M, Bengoechea O, Fermiñán E, Anduaga MF, Del Carmen S, Iglesias M, Esteban C, Angoso M, Alcazar JA, García J, Orfao A, Muñoz-Bellvis L. Genomic characterization of liver metastases from colorectal cancer patients. Oncotarget. 2016;7:72908–72922. doi: 10.18632/oncotarget.12140.
    1. Weidhaas JB, Babar I, Nallur SM, Trang P, Roush S, Boehm M, Gillespie E, Slack FJ. MicroRNAs as potential agents to alter resistance to cytotoxic anticancer therapy. Cancer Res. 2007;67:11111–11116. doi: 10.1158/0008-5472.CAN-07-2858.
    1. Yoo HI, Kim BK, Yoon SK. MicroRNA-330-5p negatively regulates ITGA5 expression in human colorectal cancer. Oncol Rep. 2016;36:3023–3029. doi: 10.3892/or.2016.5092.
    1. Chun-Zhi Z, Lei H, An-Ling Z, Yan-Chao F, Xiao Y, Guang-Xiu W, Zhi-Fan J, Pei-Yu P, Qing-Yu Z, Chun-Sheng K. MicroRNA-221 and microRNA-222 regulate gastric carcinoma cell proliferation and radioresistance by targeting PTEN. BMC Cancer. 2010;10:367. doi: 10.1186/1471-2407-10-367.
    1. Liu X, Li G, Long Z, Yin J, Zhu X, Sheng W, Huang D, Zhu H, Zhang Z, Cai H, Huang H, Zhao G, Zhou Y, Zhang Z, Wang Y. Phase II trial of preoperative chemoradiation plus perioperative SOX chemotherapy in patients with locally advanced gastric cancer. J Surg Oncol. 2018;117:692–698. doi: 10.1002/jso.24917.
    1. Chickooree D, Zhu K, Ram V, Wu HJ, He ZJ, Zhang S. A preliminary microarray assay of the miRNA expression signatures in buccal mucosa of oral submucous fibrosis patients. J Oral Pathol Med. 2016;45:691–697. doi: 10.1111/jop.12431.
    1. National Comprehensive Cancer Network . NCCN Clinical Practice Guidelines in Oncology: Gastric Cancer, V.1. 2016.
    1. Josson S, Sung SY, Lao K, Chung LW, Johnstone PA. Radiation modulation of microRNA in prostate cancer cell lines. Prostate. 2008;68:1599–1606. doi: 10.1002/pros.20827.
    1. Kato M, Paranjape T, Muller RU, Nallur S, Gillespie E, Keane K, Esquela-Kerscher A, Weidhaas JB, Slack FJ. The mir-34 microRNA is required for the DNA damage response in vivo in C. elegans and in vitro in human breast cancer cells. Oncogene. 2009;28:2419–2424. doi: 10.1038/onc.2009.106.
    1. Muralidhar B, Goldstein LD, Ng G, Winder DM, Palmer RD, Gooding EL, Barbosa-Morais NL, Mukherjee G, Thorne NP, Roberts I, Pett MR, Coleman N. Global microRNA profiles in cervical squamous cell carcinoma depend on Drosha expression levels. J Pathol. 2007;212:368–377. doi: 10.1002/path.2179.
    1. Liu Y, Xing R, Zhang X, Dong W, Zhang J, Yan Z, Li W, Cui J, Lu Y. miR-375 targets the p53 gene to regulate cellular response to ionizing radiation and etoposide in gastric cancer cells. DNA repair. 2013;12:741–750. doi: 10.1016/j.dnarep.2013.06.002.
    1. Xue Q, Sun K, Deng HJ, Lei ST, Dong JQ, Li GX. MicroRNA-338-3p inhibits colorectal carcinoma cell invasion and migration by targeting smoothened. Jpn J Clin Oncol. 2014;44:13–21. doi: 10.1093/jjco/hyt181.
    1. Yang M, Liu R, Sheng J, Liao J, Wang Y, Pan E, Guo W, Pu Y, Yin L. Differential expression profiles of microRNAs as potential biomarkers for the early diagnosis of esophageal squamous cell carcinoma. Oncol Rep. 2013;29:169–176. doi: 10.3892/or.2012.2105.
    1. Wu ZB, Li WQ, Lin SJ, Wang CD, Cai L, Lu JL, Chen YX, Su ZP, Shang HB, Yang WL, Zhao WG. MicroRNA expression profile of bromocriptine-resistant prolactinomas. Mol Cell Endocrinol. 2014;395:10–18. doi: 10.1016/j.mce.2014.07.014.
    1. Dahlhaus M, Roolf C, Ruck S, Lange S, Freund M, Junghanss C. Expression and prognostic significance of hsa-miR-142-3p in acute leukemias. Neoplasma. 2013;60:432–438. doi: 10.4149/neo_2013_056.
    1. Lin RJ, Xiao DW, Liao LD, Chen T, Xie ZF, Huang WZ, Wang WS, Jiang TF, Wu BL, Li EM, Xu LY. MiR-142-3p as a potential prognostic biomarker for esophageal squamous cell carcinoma. J Surg Oncol. 2012;105:175–182. doi: 10.1002/jso.22066.
    1. Zhang X, Yan Z, Zhang J, Gong L, Li W, Cui J, Liu Y, Gao Z, Li J, Shen L, Lu Y. Combination of hsa-miR-375 and hsa-miR-142-5p as a predictor for recurrence risk in gastric cancer patients following surgical resection. Ann Oncol. 2011;22:2257–2266. doi: 10.1093/annonc/mdq758.
    1. Maeno A, Terada N, Uegaki M, Goto T, Okada Y, Kobayashi T, Kamba T, Ogawa O, Inoue T. Up-regulation of miR-582-5p regulates cellular proliferation of prostate cancer cells under androgen-deprived conditions. Prostate. 2014;74:1604–1612. doi: 10.1002/pros.22877.
    1. Floyd DH, Zhang Y, Dey BK, Kefas B, Breit H, Marks K, Dutta A, Herold-Mende C, Synowitz M, Glass R, Abounader R, Purow BW. Novel anti-apoptotic microRNAs 582-5p and 363 promote human glioblastoma stem cell survival via direct inhibition of caspase 3, caspase 9, and Bim. PLoS One. 2014;9:e96239. doi: 10.1371/journal.pone.0096239.
    1. Uchino K, Takeshita F, Takahashi RU, Kosaka N, Fujiwara K, Naruoka H, Sonoke S, Yano J, Sasaki H, Nozawa S, Yoshiike M, Kitajima K, Chikaraishi T, Ochiya T. Therapeutic effects of microRNA-582-5p and -3p on the inhibition of bladder cancer progression. Mol Ther. 2013;21:610–619. doi: 10.1038/mt.2012.269.

Source: PubMed

Sponsorer og samarbejdspartnere

Medicinske tilstande

Narkotikainterventioner

3
Abonner