Pharmacogenomics and Personalized Medicine (Sep 2021)
miR-7, miR-10a and miR-143 Expression May Predict Response to Bevacizumab Plus Chemotherapy in Patients with Metastatic Colorectal Cancer
Abstract
Alicia Romero-Lorca,1 Apolonia Novillo,1 María Gaibar,1 María Fuencisla Gilsanz,1 Miguel Galán,1 Laura Beltrán,1 Beatriz Antón,2 Diego Malón,2 Amalia Moreno,2 Ana Fernández-Santander1 1Biomedical and Health Sciences Faculty, Universidad Europea de Madrid, Madrid, 28670, Spain; 2Department of Oncology, University Hospital of Fuenlabrada, Madrid, 28942, SpainCorrespondence: Ana Fernández-SantanderBiomedical and Health Sciences Faculty, Universidad Europea de Madrid, c/ Tajo s/n, Villaviciosa de Odón, Madrid, 28670, SpainTel +34 912 115 288Fax +34 916 168 265Email [email protected]: 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.Keywords: miRNAs, colorectal cancer, bevacizumab, paraffin-embedded biopsies, progression free survival, overall survival
