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

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). 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. 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. 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.