MiRNA expression profiling and emergence of new prognostic signature for oral squamous cell carcinoma

Christo Rajan,S Kannan,Paturu Kondaiah,Iris Himal,Shaji Thomas,Jayasree Kattoor,V G Manasa,V G Deepak Roshan,Imran Khan

doi:10.1038/s41598-021-86316-w

Abstract

Oral squamous cell carcinoma (OSCC), the most common type of head and neck cancers, is associated with high recurrence, metastasis, low long-term survival rates and poor treatment outcome. As deregulated miRNA expression plays a crucial role in malignant transformation and cancer progression, the present study is aimed at profiling the miRNA expression pattern in OSCC and developing a new miRNA prognostic signature for oral cancer. MiRNA expression profiling was performed using MiRNA microarray in 30 tumor and 18 normal samples. MiRNA signature obtained was validated with quantitative real time PCR (qRT-PCR) in 144 tumor and 36 normal samples. The potential targets, clinical implications and prognostic value of the miRNA signature were elucidated by various bioinformatics and statistical analyses. Microarray profiling identified a set of 105 miRNAs to be differentially expressed in OSCC, out of which a subset of 19 most dysregulated miRNAs were validated by qRT-PCR. In silico analysis revealed the signature miRNAs to be involved in various cancer associated pathways. Up-regulation of miR-196a, miR-21, miR-1237 and downregulation of miR-204, miR-144 was associated with poor prognosis of OSCC patients. The mir-196a/miR-204 expression ratio emerged as best predictor for disease recurrence and patient survival. Altogether, our study identified a miRNA signature for OSCC with prognostic significance.

Highlights

Oral squamous cell carcinoma (OSCC), the most common type of head and neck cancers, is associated with high recurrence, metastasis, low long-term survival rates and poor treatment outcome
The tumor specific over-expression of miR-1237 is a novel report while other signature miRNAs like miR-21, miR-424, miR-196a, miR-196b and miR-204 have been studied and reported in human cancers including OSCC20–23
The expression profiles obtained through miRNA microarray needs to be validated by an independent profiling method and TaqMan quantitative real time PCR (qRT-PCR) with its detection sensitivity, sequence specificity and reproducible quantitation stands a head[19]

Summary

Introduction

Oral squamous cell carcinoma (OSCC), the most common type of head and neck cancers, is associated with high recurrence, metastasis, low long-term survival rates and poor treatment outcome. Despite the growth in literature on miRNAs and their specific expression status across tissue and disease types, each new study brings up a new profile with very few common signatures. Besides a few tissue level miRNA expression studies, majority of the data is derived from oral cancer cell lines[12], inadequate to provide a significant picture on miRNA expression status. Addressing these issues, our study is conducted in a cohort of 144 OSCC tissue samples obtained from a region with one of the highest prevalence of OSCC in the whole of Asia. With this study we hope to bring forth a miRNA expression signature which could prove to be an effective diagnostic and prognostic marker and a potential therapeutic target

Methods

Results

Conclusion