The effectiveness of plasma miR-33a-5p as a predictive biomarker for the efficacy of colorectal cancer chemotherapy

Abstract

Several chemotherapeutic options are available for patients with metastatic colorectal cancer (mCRC), making it important to individualize treatment regimens. Individualization requires the clinical application of biomarkers for regimen selection, which is presently insufficient. miRNAs serve an important role in the control of biological processes in several types of cancer, acting as plasma biomarkers. The current study aimed to evaluate novel plasma microRNAs for predicting chemo resistance in chemotherapy for patients with colorectal cancer (CRC) by employing a Toray 3D Gene microRNA array based approach, which compared plasma content before and during treatment. Specific miRNAs that acted as biomarkers of the fluoropyrimidine (FP) + oxaliplatin (OX) + bevacizumab (BEV) regime, a common first line treatment for mCRC, were searched. The plasma samples of 110 patients with mCRC who had received the FP+OX+BEV regimen were subjected to microarray analyses using the 3D Gene miRNA microarray platform, after which miRNAs levels were quantified via reverse transcription quantitative PCR. Patients exhibiting complete response, partial response (PR) and reduced stable disease (SD) were defined as responders. Patients with extended SD and progression disease (PD) were defined as non responders. Following microarray analysis, miR 33a 5p was selected as the candidate miRNA as it was upregulated in non responder plasma samples. The expression of miR 33a 5p was upregulated in the non responders (n=15) compared with the responders (n=95) (P=0.032). The high expression group demonstrated significantly poor progression free survival (P<0.01). To evaluate whether miR 33a 5p can serve as a marker of chemo resistance, miR 33a 5p expression levels were assessed at the following three time points: Pre point (before chemotherapy); PR point (3 months after chemotherapy began); and PD point (the time at which recurrence or progression was recorded). The results revealed that expression levels were significantly increased at the PD point when compared with that at the pre point (P=0.024). The current study determined that the miR 33a 5p expression level in the plasma may serve as a predictive marker of efficacy and as a biomarker of chemo resistance.