Aberrant Methylation of RASSF1A Closely Associated with HNSCC, a Meta-Analysis.

Rui-Wei Meng,Xun Niu,Xiong Chen,Yang-Xin Huang,Mei-Xia Lu,Yun-Cheng Li,Dan-Dan Du,Cheng Lu,Hao Shi

doi:10.1038/srep20756

Abstract

The RAS association domain family protein 1a (RASSF1A), a tumor suppressor gene at 3p21.3, plays a very important role in various cancers, including the head and neck squamous cell carcinoma (HNSCC). Hypermethylation of CpG islands in the RASSF1A promoter region contribute to epigenetic inactivation. However, the association between RASSF1A promoter methylation and HNSCC remains unclear and controversial. Therefore, a meta-analysis was performed in the study to identify the association. We identified the eligible studies through searching PubMed, EMBASE, Web of Science, and China National Knowledge Infrastructure (CNKI) databases with a systematic searching strategy. The information on characteristics of each study and prevalence of RASSF1A methylation were collected. Pooled odds ratios (ORs) with corresponding confidence intervals (CIs) were calculated. Meta-regression was performed to analyze heterogeneity and funnel plots were applied to evaluate publication bias. A total of 550 HNSCC patients and 404 controls from twelve eligible studies were included in the meta-analysis. Overall, a significant association was observed between RASSF1A methylation status and HNSCC risk under a random-effects model (OR = 2.93, 95% CI: 1.58–5.46). There was no significant publication bias observed. The meta-analysis suggested that there was a significant association between aberrant RASSF1A methylation and HNSCC.

Highlights

Head and neck cancer is the sixth most common cancer worldwide accounting for approximately 6% of all newly diagnosed malignancies
All of these findings indicate that RAS association domain family protein 1a (RASSF1A) might play an important role in the development of head and neck squamous cell carcinoma (HNSCC)
Increased methylation in the promoter region of tumor suppressor gene can account for a progressive reduction of its expression, silencing and selective proliferative advantage in certain cells, which plays a vital role in the development of human cancer[39]

Summary

Introduction

Head and neck cancer is the sixth most common cancer worldwide accounting for approximately 6% of all newly diagnosed malignancies. Teschendorff[5] observed that invasive cancers displayed increased DNA methylation at the risk CpG sites in contrast to normal tissue, but lower levels in contrast to pre-cancerous lesions. Hypermethylation of RASSF1A within promoter CpG islands is frequently observed in the HNSCC cell lines[22]. All of these findings indicate that RASSF1A might play an important role in the development of HNSCC. A number of studies have investigated the association between aberrant methylation of RASSF1A and HNSCC through a comparison of the methylation prevalence of RASSF1A between cancerous tissues and controls. We conducted a meta-analysis of 12 published studies to conclude the association

Methods

Results

Conclusion