MicroRNAs as outcome predictors in patients with metastatic colorectal cancer treated with bevacizumab in combination with FOLFOX

Abstract

Bevacizumab is a humanized anti-vascular endothelial growth factor monoclonal antibody, used in combination with a oxaliplatin-based chemotherapy in the treatment of metastatic colorectal cancer (mCRC). The aim of the present study was to identify microRNA (miRNA)-based predictive biomarkers of therapy response in order to avoid unnecessary and costly therapy to non-responding patients. High-throughput miRNA microarray profiling (Affymetrix miRNA array) was performed on a discovery cohort of patients with mCRC. The discovery cohort was (n=20) divided into either responding (n=10) or non-responding (n=10) groups of bevacizumab/5-flourouracil, leucovorin, oxaliplatin (FOLFOX) treatment according to Response Evaluation Criteria in Solid Tumors criteria. Validation of candidate miRNAs was performed on an independent cohort of 41 patients with mCRC using quantitative reverse transcription polymerase chain reaction. Normalized data were subjected to receiver operating characteristic and Kaplan-Meier analyses. In total, 67 miRNAs were identified to be differentially expressed when miRNA expression was compared between responding and non-responding patients to bevacizumab/FOLFOX treatment (P<0.05). A total of 7 miRNAs were chosen for independent validation, which confirmed significantly higher expression of miR-92b-3p, miR-3156-5p, miR-10a-5p and miR-125a-5p (P<0.005) in tumor tissue of responding patients compared with non-reponding patients. Using the combination of miRNAs, the present study identified responders to the therapy with sensitivity 82% and specificity 64% (area under the curve = 0.8015). In conclusion, 4 predictive miRNAs associated with progression-free survival (PFS) were identified in patients with mCRC treated with bevacizumab/FOLFOX. Following further independent validations, detection of these miRNA may enable identification of patients with mCRC who may potentially benefit from the therapy.

Retracted: Epigenetic silenced miR‐125a‐5p could be self‐activated through targeting Suv39H1 in gastric cancer

“…These data showed that overexpressing Furthermore, miR-125a-5p has been validated to prevent the cancer cell progression. [10][11][12][13][14][15][16][17][18][19]23,24 However, the underlying mechanism of the low expression of miR-125a-5p in gastric cancer remains unknown.…”

miRNA expression changes during the course of neoadjuvant bevacizumab and chemotherapy treatment in breast cancer

“…Studies have demonstrated a role for miRNAs in resistance or sensitization of tumors to chemotherapy and radiotherapy. Previous studies have looked at miRNA´s role as predictors for antiangiogenic therapy by comparing their expression in responders vs. nonresponders either before or after treatment (Kiss et al , ), or changes in the level of circulating miRNAs (Hansen et al , ). The present study is, to our knowledge, the first study to address the changes in miRNA expression within the tumor over the course of treatment, and their correlation to response.…”

“…miRNAs have also been shown to have pro‐angiogenic effects (i.e., the miR‐17‐92 cluster (Suarez et al , ), miR‐21 (Liu et al , ), and miR‐378 (Lee et al , )) or antiangiogenic effects (i.e., miR‐221 and miR‐222 (Poliseno et al , )). Studies in colorectal cancer, glioblastoma, and ovarian cancer have identified miRNAs with potential as predictors for antiangiogenic therapy by comparing expression levels in responders vs. nonresponders in surgical resections from the primary tumor before or after treatment (Chan et al , ; Hayes et al , ; Kiss et al , ). Changes in circulating miRNAs have also been assessed, where miR‐126 has been shown to predict response in patients with metastatic colorectal cancer during chemotherapy and Bev treatment (Hansen et al , ).…”

MicroRNAs (miRNAs) in Colorectal Cancer

“…miR-92b-3p, miR-3156-5p, miR-10a-5p, and miR-125a-5 were found to be related with progression-free survival in meta;static CRC patients treated with 5-FU/oxaliplatin/bevacizumab regime [90]. A negative relationship was found between miR-27b, miR-148a, and miR-326 expression levels and progression-free survival in metastatic colorectal cancer patients receiving first-line oxaliplatinbased treatment [91].…”