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International Journal of Colorectal Disease
Published in: International Journal of Colorectal Disease 11/2019

01-11-2019 | Colorectal Cancer | Original Article

MiR-218 and miR-100 polymorphisms as markers of irinotecan-based chemotherapy response in metastatic colorectal cancer

Authors: Dimitra-Ioanna Lampropoulou, Gerasimos Aravantinos, Konstantinos Laschos, Theodosis Theodosopoulos, Christos Papadimitriou, Maria Gazouli

Published in: International Journal of Colorectal Disease | Issue 11/2019

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Abstract

Purpose

Colorectal cancer is the fourth cause of cancer-related death. Drug toxicity and resistance remain concerns of major importance. miR-100 and miR-218 are micro-RNAs that regulate cellular proliferation, differentiation and apoptosis acting as oncogenes and tumour suppressors; their functions and have been linked with toxicity development and drug resistance.

Methods

We investigated the correlation between rs11134527 miR-218 and rs1834306 miR-100 polymorphisms and irinotecan-based regimens with regard to drug efficacy and toxicity. A total of 105 mCRC patients receiving irinotecan-based regimens were included in our study and assessed in terms of toxicity development and response to treatment. Rs11134527 miR-218 and rs1834306 miR-100 polymorphism genotyping in the peripheral blood was performed with PCR-RFLP.

Results

Neither rs11134527 miR-218 nor rs1834306 miR-100 are associated with toxicity risk to treatment regimens. GA/AA genotypes of rs11134527 and CT/TT genotypes of rs1834306 were associated with a significantly reduced time-to-progression (TTP) and overall survival (OS).

Conclusions

GA/AA genotypes of rs11134527 miR-218 and CT/TT genotypes of rs1834306 miR-100 polymorphisms could serve as prognostic biomarkers of TTP and OS. Carriers of the A allele of the miR-218 rs11134527 and T allele of the miR-100 rs1834306 polymorphisms are more likely not to respond to irinotecan-based therapies. However, further studies in larger patient populations are required.
Literature
1.
Favoriti P, Carbone G, Greco M, Pirozzi F, Pirozzi RE, Corcione F (2016) Worldwide burden of colorectal cancer: a review. Updat Surg 68:7–11CrossRef
2.
Kopetz S, Chang GJ, Overman MJ, Eng C, Sargent DJ, Larson DW, Grothey A, Vauthey JN, Nagorney DM, McWilliams RR (2009) Improved survival in metastatic colorectal cancer is associated with adoption of hepatic resection and improved chemotherapy. J Clin Oncol 27:3677–3683PubMedPubMedCentralCrossRef
3.
Zheng T, Wang J, Chen X, Liu L (2010) Role of microRNA in anticancer drug resistance. Int J Cancer 126:2–10PubMedCrossRef
4.
Tsuchiya Y, Nakajima M, Takagi S, Taniya T, Yokoi T (2006) MicroRNA regulates the expression of human cytochrome P450 1B1. Cancer Res 66:9090–9098PubMedCrossRef
5.
Vergani E, Di Guardo L, Dugo M, Rigoletto S, Tragni G, Ruggeri R, Perrone F, Tamborini E, Gloghini A, Arienti F, Vergani B, Deho P, De Cecco L, Vallacchi V, Frati P, Shahaj E, Villa A, Santinami M, De Braud F, Rivoltini L, Rodolfo M (2016) Overcoming melanoma resistance to vemurafenib by targeting CCL2-induced miR-34a, miR-100 and miR-125b. Oncotarget. 7:4428–4441PubMedCrossRef
6.
Hu Y, Xu K, Yagüe E (2015) miR-218 targets survivin and regulates resistance to chemotherapeutics in breast cancer. Breast Cancer Res Treat 151:269–280PubMedCrossRef
7.
Lu Y, Zhao X, Liu Q, Li C, Graves-Deal R, Cao Z, Singh B, Franklin JL, Wang J, Hu H, Wei T, Yang M, Yeatman TJ, Lee E, Saito-Diaz K, Hinger S, Patton JG, Chung CH, Emmrich S, Klusmann JH, Fan D, Coffey RJ (2017) lncRNA MIR100HG-derived miR-100 and miR-125b mediate cetuximab resistance via Wnt/β-catenin signaling. Nat Med 23:1331–1341PubMedPubMedCentralCrossRef
8.
Chen P, Zhao X, Ma L (2013) Downregulation of microRNA-100 correlates with tumor progression and poor prognosis in hepatocellular carcinoma. Mol Cell Biochem 383:49–58PubMedCrossRef
9.
Henson BJ, Bhattacharjee S, O’Dee DM, Feingold E, Gollin SM (2009) Decreased expression of miR-125b and miR-100 in oral cancer cells contributes to malignancy. Genes Chromosom Cancer 48:569–582PubMedCrossRef
10.
Wang G, Chen L, Meng J, Chen M, Zhuang L, Zhang L (2013) Overexpression of microRNA-100 predicts an unfavorable prognosis in renal cell carcinoma. Int Urol Nephrol 45:373–379PubMedCrossRef
11.
Chen P, Xi Q, Wang Q, Wei P (2014) Downregulation of microRNA-100 correlates with tumor progression and poor prognosis in colorectal cancer. Med Oncol 31:235PubMedCrossRef
12.
Fujino Y, Takeishi S, Nishida K, Okamoto K, Muguruma N, Kimura T, Kitamura S, Miyamoto H, Fujimoto A, Higashijima J, Shimada M, Rokutan K, Takayama T (2017) Downregulation of microRNA-100/microRNA-125b is associated with lymph node metastasis in early colorectal cancer with submucosal invasion. Cancer Sci 108:390–397PubMedPubMedCentralCrossRef
13.
Boni V, Zarate R, Villa JC, Bandrés E, Gomez MA, Maiello E, Garcia-Foncillas J, Aranda E (2011) Role of primary miRNA polymorphic variants in metastatic colon cancer patients treated with 5-fluorouracil and irinotecan. Pharm J 11:429–436
14.
Yang XD, Xu X, Zhang SY, Wu Y, Xing CG, Ru G, Xu HT, Cao JP (2015) Role of miR-100 in the radioresistance of colorectal cancer cells. Am J Cancer Res 5:545–559PubMedPubMedCentral
15.
Yamamoto N, Kinoshita T, Nohata N, Itesako T, Yoshino H, Enokida H, Nakagawa M, Shozu M, Seki N (2013) Tumor suppressive microRNA-218 inhibits cancer cell migration and invasion by targeting focal adhesion pathways in cervical squamous cell carcinoma. Int J Oncol 42:1523–1532PubMedPubMedCentralCrossRef
16.
Zhu Z, Xu Y, Du J, Tan J, Jiao H (2014) Expression of MicroRNA-218 in human pancreatic ductal adenocarcinoma and its correlation with tumor progression and patient survival. J Surg Oncol 109:89–94PubMedCrossRef
17.
Jiang L, Wang C, Sun C, Xu Y, Ding Z, Zhang X, Huang J, Yu H (2014) The impact of pri-miR-218 rs11134527 on the risk and prognosis of patients with esophageal squamous cell carcinoma. Int J Clin Exp Pathol 7:6206–6212PubMedPubMedCentral
18.
Shi TY, Chen XJ, Zhu ML, Wang MY, He J, Yu KD, Shao ZM, Sun MH, Zhou XY, Cheng X, Wu X, Wei Q (2013) A pri-miR-218 variant and risk of cervical carcinoma in Chinese women. BMC Cancer 13:19PubMedPubMedCentralCrossRef
19.
Li C, Zhang Y, Li Y, Ma Q, Liu S, Yao Y, Tan F, Shi L, Yao Y (2018) The association of polymorphisms in miRNAs with nonsmall cell lung cancer in a Han Chinese population. Cancer Manag Res 10:697–704PubMedPubMedCentralCrossRef
20.
Danesh H, Hashemi M, Bizhani F, Hashemi SM, Bahari G (2018) Association study of miR-100, miR-124-1, miR-218-2, miR-301b, miR-605, and miR-4293 polymorphisms and the risk of breast cancer in a sample of Iranian population. Gene. 647:73–78PubMedCrossRef
21.
Moazeni-Roodi A, Bahari G, Taheri M, Ansari H, Hashemi M (2018) Association between miR-218 rs11134527 polymorphism and risk of selected types of cancer in Asian population: an updated metaanalysis of case-control studies. Gene. 678:370–376PubMedCrossRef
22.
23.
Zhou X, Qu Z, Zhu C, Lin Z, Huo Y, Wang X, Wang J, Li B (2016) Identification of urinary microRNA biomarkers for detection of gentamicin-induced acute kidney injury in rats. Regul Toxicol Pharmacol 78:78–84PubMedCrossRef
24.
Li P, Zhang X, Wang L, Du L, Yang Y, Liu T, Li C, Wang C (2017) lncRNA HOTAIR contributes to 5FU resistance through suppressing miR-218 and activating NF-κB/TS signaling in colorectal cancer. Mol Ther Nucleic Acids 8:356–369PubMedPubMedCentralCrossRef
25.
Ratain MJ (2002) Irinotecan dosing: does the CPT in CPT-11 stand for “Can’t predict toxicity”? J Clin Oncol 20:7–8PubMedCrossRef
26.
Toffoli G, Cecchin E, Corona G, Russo A, Buonadonna A, D’Andrea M, Pasetto LM, Pessa S, Errante D, De Pangher V, Giusto M, Medici M, Gaion F, Sandri P, Galligioni E, Bonura S, Boccalon M, Biason P, Frustaci S (2006) The role of UGT1A1*28 polymorphism in the pharmacodynamics and pharmacokinetics of irinotecan in patients with metastatic colorectal cancer. J Clin Oncol 24:3061–3068PubMedCrossRef
27.
Van Cutsem E, Cervantes A, Adam R, Sobrero A, Van Krieken JH, Aderka D, Aranda Aguilar E, Bardelli A, Benson A, Bodoky G, Ciardiello F, D'Hoore A, Diaz-Rubio E, Douillard JY, Ducreux M, Falcone A, Grothey A, Gruenberger T, Haustermans K, Heinemann V, Hoff P, Köhne CH, Labianca R, Laurent-Puig P, Ma B, Maughan T, Muro K, Normanno N, Österlund P, Oyen WJ, Papamichael D, Pentheroudakis G, Pfeiffer P, Price TJ, Punt C, Ricke J, Roth A, Salazar R, Scheithauer W, Schmoll HJ, Tabernero J, Taïeb J, Tejpar S, Wasan H, Yoshino T, Zaanan A, Arnold D (2016) ESMO consensus guidelines for the management of patients with metastatic colorectal cancer. Ann Oncol 27:1386–1422PubMedCrossRef
28.
Saltz LB, Clarke S, Diaz-Rubio E, Scheithauer W, Figer A, Wong R, Koski S, Lichinitser M, Yang TS, Rivera F, Couture F, Sirzén F, Cassidy J (2008) Bevacizumab in combination with oxaliplatin-based chemotherapy as first-line therapy in metastatic colorectal cancer: a randomized phase III study. J Clin Oncol 26:2013–2019PubMedCrossRef
29.
Ciardiello F, Lenz HJ, Kohne CH, Heinemann V, Tejpar S, Esser R (2014) Effect of KRAS and NRAS mutational status on first-line treatment with FOLFIRI plus cetuximab in patients with metastatic colorectal cancer (mCRC): new results from the CRYSTAL trial. J Clin Oncol 32:3_suppl, LBA443-LBA443CrossRef
30.
Seymoyr MT, Brown SR, Middleton G, Maughan T, Richman S, Gwyther S, Lowe C, Seligmann JF, Wadsley J, Maisey N, Chau I, Hill M, Dawson L, Falk S, O'Callaghan A, Benstead K, Chambers P, Oliver A, Marshall H, Napp V, Quirke P (2013) Panitumumab and irinotecan versus irinotecan alone for patients with KRAS wild- type, fluorouracil-resistant advanced colorectal cancer (PICCOLO): a prospectively stratified randomised trial. Lancet Oncol 14:749–759CrossRef
31.
Dervenis C, Xynos E, Sotiropoulos G, Gouvas N, Boukovinas I, Agalianos C, Androulakis N, Athanasiadis A, Christodoulou C, Chrysou E, Emmanouilidis C, Georgiou P, Karachaliou N, Katopodi O, Kountourakis P, Kyriazanos I, Makatsoris T, Papakostas P, Papamichael D, Pechlivanides G, Pentheroudakis G, Pilpilidis I, Sgouros J, Tekkis P, Triantopoulou C, Tzardi M, Vassiliou V, Vini L, Xynogalos S, Ziras N, Souglakos J (2016) Clinical practice guidelines for the management of metastatic colorectal cancer: a consensus statement of the Hellenic Society of Medical Oncologists (HeSMO). Ann Gastroenterol 29:390–416PubMedPubMedCentral
32.
Lampropoulou DI, Aravantinos G, Katifelis H, Lazaris F, Laschos K, Theodosopoulos T, Papadimitriou C, Gazouli M (2019) Long non-coding RNA polymorphisms and prediction of response to chemotherapy based on irinotecan in patients with metastatic colorectal cancer. Cancer Biomark 25:213–221PubMedCrossRef
33.
Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Jänne PA, Johnson BE, Van den Abbeele AD (2009) New response evaluation criteria in solid tumors: revised RECIST guideline (version 1.1). Eur J Cancer 45:228–247CrossRefPubMed
34.
35.
Isaakidiou A, Gazouli M, Aravantinos G, Pectasides D, Theodoropoulos GE (2016) Prediction of response to combination chemotherapy with irinotecan in Greek patients with metastatic colorectal cancer. J Cancer Res Ther 12:193–197CrossRef
36.
Zhuang Z, Hu F, Hu J, Wang C, Hou J, Yu Z, Wang TT, Liu X, Huang H (2017) MicroRNA-218 promotes cisplatin resistance in oral cancer via the PPP2R5A/Wnt signaling pathway. Oncol Rep 38:2051–2061PubMedPubMedCentralCrossRef
37.
Zhu J, Yang L, You W, Cui X, Chen Y, Hu J, Liu W, Li S, Song X, Wei Y, Zhang W, Li F (2015) Genetic variation in miR-100 rs1834306 is associated with decreased risk for esophageal squamous cell carcinoma in Kazakh patients in northwest China. Int J Clin Exp Pathol 8:7332–7340PubMedPubMedCentral
38.
Motawi TK, Mady AE, Shaheen S, Elshenawy SZ, Talaat RM, Rizk SM (2019) Genetic variation in microRNA-100 (miR-100) rs1834306 T/C associated with hepatitis B virus (HBV) infection: correlation with expression level. Infect Genet Evol 73:444–449PubMedCrossRef
39.
Gao X, Yang L, Ma Y, Yang J, Zhang G, Huang G, Huang Q, Chen L, Fu F, Chen Y, Su D, Dong Y, Ma X, Lu C, Peng X (2013) No association of functional variant in pri-miR-218 and risk of congenital heart disease in a Chinese population. Gene. 523:173–177PubMedCrossRef
40.
Scartozzi M, Bearzi I, Pierantoni C, Mandolesi A, Loupakis F, Zaniboni A, Catalano V, Quadri A, Zorzi F, Berardi R, Biscotti T, Labianca R, Falcone A, Cascinu S (2007) Nuclear factor-kB tumor expression predicts response and survival in irinotecan-refractory metastatic colorectal cancer treated with cetuximab-irinotecan therapy. J Clin Oncol 25:3930–3935PubMedCrossRef
41.
Wu C, Li M, Hu C, Duan H (2014) Prognostic role of microRNA polymorphisms in patients with advanced esophageal squamous cell carcinoma receiving platinum-based chemotherapy. Cancer Chemother Pharmacol 73:335–341PubMedCrossRef
42.
Chen Z, Wu L, Lin Q, Shi J, Lin X, Shi L (2016) Evaluation of miR-182/miR-100 ratio for diagnosis and survival prediction in bladder cancer. Arch Iran Med 19:645–651PubMed
43.
Stenholm L, Stoehlmacher-Williams J, Al-Batran SE, Heussen N, Akin S, Pauligk C, Lehmann S, Senff T, Hofheinz RD, Ehninger G, Kramer M, Goekkurt E (2013) Prognostic role of microRNA polymorphisms in advanced gastric cancer: a translational study of the Arbeitsgemeinschaft Internistische Onkologie (AIO). Ann Oncol 24:2581–2588PubMedCrossRef
Metadata
Title
MiR-218 and miR-100 polymorphisms as markers of irinotecan-based chemotherapy response in metastatic colorectal cancer
Authors
Dimitra-Ioanna Lampropoulou
Gerasimos Aravantinos
Konstantinos Laschos
Theodosis Theodosopoulos
Christos Papadimitriou
Maria Gazouli
Publication date
01-11-2019
Publisher
Springer Berlin Heidelberg
Published in
International Journal of Colorectal Disease / Issue 11/2019
Print ISSN: 0179-1958
Electronic ISSN: 1432-1262
DOI
https://doi.org/10.1007/s00384-019-03401-3

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