miRNA-200c and miRNA-141 as potential prognostic biomarkers and regulators of epithelial-mesenchymal transition in eyelid sebaceous gland carcinoma.

Abstract

MicroRNA (miRNA)-200c and miRNA-141 are tumour suppressors, which regulate epithelial-mesenchymal transition (EMT), leading to tumour invasion and metastasis in various malignancies. miRNA-200c and miRNA-141 maintain the epithelial phenotype by post-transcriptionally inhibiting the E-cadherin repressors, zinc finger E-box binding homeobox (ZEB)1 and ZEB2. The present study was performed to determine the prognostic significance of miRNA-200c and miRNA-141, and their association with EMT markers ZEB1, ZEB2 and E-cadherin in eyelid sebaceous gland carcinoma (SGC). Expression levels of miRNA-200c and miRNA-141 were determined in 42 eyelid SGC cases by quantitative real-time PCR (qPCR). Their association with ZEB1, ZEB2 and E-cadherin was determined by qPCR and immunohistochemistry. Kaplan-Meier plots and Spearman's rank correlation tests were applied to analyse the data. Patients were followed up for 7-44 months. Low expression levels of miRNA-200c and miRNA-141 were seen in 36/42 (86%) and 28/42 (67%) cases, respectively. Low miRNA-200c correlated significantly with large tumour size (p=0.03) and poor differentiation (p=0.03). Low miRNA-141 correlated significantly with large tumour size (p=0.02) and lymph node metastasis (p=0.04). Survival analysis revealed that patients with low miRNA-200c (p<0.05) and miRNA-141 expression (p=0.07) had shorter disease-free survival. There was a significant association of both miRNA-200c and miRNA-141 with E-cadherin and ZEB2 expression. Low levels of miRNA-200c and miRNA-141 in patients with eyelid SGC facilitates tumour progression by promoting EMT and miRNA-200c has emerged as a novel potential predictor of survival.