MiR-7, MiR-10a and MiR-143 Expression May Predict Response to Bevacizumab Plus Chemotherapy in Patients with Metastatic Colorectal Cancer

Overview

Journal Pharmgenomics Pers Med

Publisher Dove Medical Press

Date 2021 Oct 7

PMID 34616173

Citations 7

Authors

Alicia Romero-Lorca

Apolonia Novillo

Maria Gaibar

Maria Fuencisla Gilsanz

Miguel Galan

Laura Beltran

Beatriz Anton

Diego Malon

Amalia Moreno

Ana Fernandez-Santander

Affiliations

Soon will be listed here.

Abstract

Purpose: Bevacizumab is a monoclonal antibody that binds to vascular endothelial growth factor A. It is currently used in combination with chemotherapy to treat metastatic colorectal cancer. This therapy is not equally effective in every patient; in some, mechanisms of resistance arise that remain poorly understood. The aim of the present work was to determine whether the expression of 26 miRNAs could be associated with the effectiveness of bevacizumab plus chemotherapy, with progression-free survival (PFS), and with overall survival (OS) in metastatic colorectal cancer.

Patients And Methods: Paraffin-embedded biopsies from 76 patients with metastatic colorectal cancer were collected to isolate miRNAs. The expression of 26 miRNAs was analyzed by quantitative RT-PCR. For the purpose of analysis, patients were classified as either "responders" (PFS ≥6 months since beginning treatment) or "non-responders" (PFS <6 months). For the analysis of PFS and OS, patients were classified into two groups using the median gene expression value as the cut-off point ("high" [≥50% percentile] or "low" [<50% percentile]). Time-to-event data were analyzed using the Kaplan-Meier method and compared by the log rank test. Cox regression was used to estimate hazard ratios (HR) and their 95% confidence intervals.

Results: miR-7-5p and miR-10a-5p were more strongly expressed in non-responders than responders (p=0.049 and p=0.043, respectively), and OS was poorer in patients showing these higher expression levels (HR=2.54, 95% CI 1.42-4.55, p=0. 001, and HR=1.81, 95% CI 1.02-3.20, p=0.039, respectively). The overexpression of miR-143-3p, however, was associated with a better prognosis and significantly better PFS (HR=0.57; 95% CI: 0.33-0.96; p=0.033).

Conclusion: High expression values for miR-7-5p and miR-10a-5p might be considered markers of a poorer prognosis in patients with metastatic colorectal cancer treated with bevacizumab plus chemotherapy, while the same for miR-143-3p might be a marker of better outcomes.

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References

Xiong G, Huang H, Feng M, Yang G, Zheng S, You L . MiR-10a-5p targets TFAP2C to promote gemcitabine resistance in pancreatic ductal adenocarcinoma. J Exp Clin Cancer Res. 2018; 37(1):76. PMC: 5883523. DOI: 10.1186/s13046-018-0739-x. View

Suto T, Yokobori T, Yajima R, Morita H, Fujii T, Yamaguchi S . MicroRNA-7 expression in colorectal cancer is associated with poor prognosis and regulates cetuximab sensitivity via EGFR regulation. Carcinogenesis. 2014; 36(3):338-45. DOI: 10.1093/carcin/bgu242. View

Wang X, Ling C, Li L, Qin Y, Qi J, Liu X . MicroRNA-10a/10b represses a novel target gene mib1 to regulate angiogenesis. Cardiovasc Res. 2016; 110(1):140-50. DOI: 10.1093/cvr/cvw023. View

Yu T, Liu L, Li J, Yan M, Lin H, Liu Y . MiRNA-10a is upregulated in NSCLC and may promote cancer by targeting PTEN. Oncotarget. 2015; 6(30):30239-50. PMC: 4745794. DOI: 10.18632/oncotarget.4972. View

Giles K, Brown R, Epis M, Kalinowski F, Leedman P . miRNA-7-5p inhibits melanoma cell migration and invasion. Biochem Biophys Res Commun. 2012; 430(2):706-10. DOI: 10.1016/j.bbrc.2012.11.086. View

Kiss I, Mlcochova J, Souckova K, Fabian P, Poprach A, Halamkova J . MicroRNAs as outcome predictors in patients with metastatic colorectal cancer treated with bevacizumab in combination with FOLFOX. Oncol Lett. 2017; 14(1):743-750. PMC: 5494676. DOI: 10.3892/ol.2017.6255. View

Garcia J, Hurwitz H, Sandler A, Miles D, Coleman R, Deurloo R . Bevacizumab (Avastin®) in cancer treatment: A review of 15 years of clinical experience and future outlook. Cancer Treat Rev. 2020; 86:102017. DOI: 10.1016/j.ctrv.2020.102017. View

Moreno E, Pascual A, Prieto-Cuadra D, Laza V, Molina-Cerrillo J, Ramos-Munoz M . Novel Molecular Characterization of Colorectal Primary Tumors Based on miRNAs. Cancers (Basel). 2019; 11(3). PMC: 6468580. DOI: 10.3390/cancers11030346. View

Hassel D, Cheng P, White M, Ivey K, Kroll J, Augustin H . MicroRNA-10 regulates the angiogenic behavior of zebrafish and human endothelial cells by promoting vascular endothelial growth factor signaling. Circ Res. 2012; 111(11):1421-33. PMC: 3525481. DOI: 10.1161/CIRCRESAHA.112.279711. View

10.

Chang C, Fan T, Yu J, Liao G, Lin Y, Shih A . The prognostic significance of RUNX2 and miR-10a/10b and their inter-relationship in breast cancer. J Transl Med. 2014; 12:257. PMC: 4189660. DOI: 10.1186/s12967-014-0257-3. View

11.

Pratama M, Pascut D, Massi M, Tiribelli C . The role of microRNA in the resistance to treatment of hepatocellular carcinoma. Ann Transl Med. 2019; 7(20):577. PMC: 6861820. DOI: 10.21037/atm.2019.09.142. View

12.

Zhi Y, Xie X, Wang R, Wang B, Gu W, Ling Y . Serum level of miR-10-5p as a prognostic biomarker for acute myeloid leukemia. Int J Hematol. 2015; 102(3):296-303. DOI: 10.1007/s12185-015-1829-6. View

13.

Son J, Jeong H, Park D, No S, Lee E, Lee J . miR-10a and miR-204 as a Potential Prognostic Indicator in Low-Grade Gliomas. Cancer Inform. 2017; 16:1176935117702878. PMC: 5397276. DOI: 10.1177/1176935117702878. View

14.

Jia H, Zhang Z, Zou D, Wang B, Yan Y, Luo M . MicroRNA-10a is down-regulated by DNA methylation and functions as a tumor suppressor in gastric cancer cells. PLoS One. 2014; 9(1):e88057. PMC: 3909310. DOI: 10.1371/journal.pone.0088057. View

15.

Long M, Wu F, Li P, Liu M, Li X, Tang H . MicroRNA-10a targets CHL1 and promotes cell growth, migration and invasion in human cervical cancer cells. Cancer Lett. 2012; 324(2):186-96. DOI: 10.1016/j.canlet.2012.05.022. View

16.

Sun W, Ma Y, Chen P, Wang D . MicroRNA-10a silencing reverses cisplatin resistance in the A549/cisplatin human lung cancer cell line via the transforming growth factor-β/Smad2/STAT3/STAT5 pathway. Mol Med Rep. 2015; 11(5):3854-9. DOI: 10.3892/mmr.2015.3181. View

17.

Meng X, Joosse S, Muller V, Trillsch F, Milde-Langosch K, Mahner S . Diagnostic and prognostic potential of serum miR-7, miR-16, miR-25, miR-93, miR-182, miR-376a and miR-429 in ovarian cancer patients. Br J Cancer. 2015; 113(9):1358-66. PMC: 4815782. DOI: 10.1038/bjc.2015.340. View

18.

Lujambio A, Lowe S . The microcosmos of cancer. Nature. 2012; 482(7385):347-55. PMC: 3509753. DOI: 10.1038/nature10888. View

19.

Shi Y, Luo X, Li P, Tan J, Wang X, Xiang T . miR-7-5p suppresses cell proliferation and induces apoptosis of breast cancer cells mainly by targeting REGγ. Cancer Lett. 2014; 358(1):27-36. DOI: 10.1016/j.canlet.2014.12.014. View

20.

Nagano Y, Toiyama Y, Okugawa Y, Imaoka H, Fujikawa H, Yasuda H . MicroRNA-7 Is Associated with Malignant Potential and Poor Prognosis in Human Colorectal Cancer. Anticancer Res. 2016; 36(12):6521-6526. DOI: 10.21873/anticanres.11253. View