High microRNA-28-5p expression in colorectal adenocarcinoma predicts short-term relapse of node-negative patients and poor overall survival of patients with non-metastatic disease

Abstract

Abstract Background: MicroRNAs (miRNAs) may function either as oncogenes or tumor suppressors and are heavily involved in the initiation and progression of cancer, and in metastasis of tumor cells. MicroRNA-28-5p (miR-28-5p) targets several cancer-related genes and is hence involved in cell proliferation, migration, invasion and epithelial-mesenchymal transition. In this study, we investigated the potential diagnostic and prognostic significance of miR-28-5p expression in colorectal adenocarcinoma, the most frequent type of colorectal cancer (CRC). Methods: Therefore, we isolated total RNA from 182 colorectal adenocarcinoma specimens and 86 paired non-cancerous colorectal mucosae. After polyadenylation of 2 μg total RNA and its reverse transcription using an oligo-dT-adapter primer, we quantified miR-28-5p levels using an in-house-developed reverse-transcription real-time quantitative polymerase chain reaction (RT-qPCR) method, based on the SYBR Green chemistry. Results: Comparison of miR-28-5p levels among 86 pairs of colorectal tumors and their adjacent non-cancerous mucosae uncovered the downregulation of miR-28-5p expression in the majority of malignant colorectal tumors. More importantly, high miR-28-5p expression predicts poor disease-free survival (DFS) and overall survival (OS) of colorectal adenocarcinoma patients. Multivariate Cox regression analysis revealed that miR-28-5p overexpression is a significant predictor of poor prognosis in colorectal adenocarcinoma, independent of tumor size, histological grade, TNM staging, radiotherapy and chemotherapy. Interestingly, strong miR-28-5p expression retains its predictive potential regarding relapse among patients with negative regional lymph nodes, and predicts poor OS in patients diagnosed with non-metastatic colorectal adenocarcinoma. Conclusions: High miR-28-5p expression predicts poor DFS and OS of colorectal adenocarcinoma patients, independently of clinicopathological prognosticators and standard patient treatment, including radiotherapy and chemotherapy.