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The relationship between RASSF1A promoter methylation and thyroid carcinoma: A meta-analysis of 14 articles and a

Heng Niu¹, Jingyu Yang, Kunxian Yang

¹aChest Surgery, The First People's Hospital of Yunnan Province, Kunming, Yunnan bLandscape Laboratory, Guilin, Guangxi, China.

|November 18, 2017

Abstract

Background:

DNA promoter methylation can suppresses gene expression and shows an important role in the biological functions of Ras association domain family 1A (RASSF1A). Many studies have performed to elucidate the role of RASSF1A promoter methylation in thyroid carcinoma, while the results were conflicting and heterogeneous. Here, we analyzed the data of databases to determine the relationship between RASSF1A promoter methylation and thyroid carcinoma.

Methods:

We used the data from 14 cancer-normal studies and Gene Expression Omnibus (GEO) database to analyze RASSF1A promoter methylation in thyroid carcinoma susceptibility. The data from the Cancer Genome Atlas project (TCGA) database was used to analyze the relationship between RASSF1A promoter methylation and thyroid carcinoma susceptibility, clinical characteristics, prognosis. Odds ratios were estimated for thyroid carcinoma susceptibility and hazard ratios were estimated for thyroid carcinoma prognosis. The heterogeneity between studies of meta-analysis was explored using H, I values, and meta-regression. We adopted quality criteria to classify the studies of meta-analysis. Subgroup analyses were done for thyroid carcinoma susceptibility according to ethnicity, methods, and primers.

Results:

Result of meta-analysis indicated that RASSF1A promoter methylation is associated with higher susceptibility to thyroid carcinoma with small heterogeneity. Similarly, the result from GEO database also showed that a significant association between RASSF1A gene promoter methylation and thyroid carcinoma susceptibility. For the results of TCGA database, we found that RASSF1A promoter methylation is associated with susceptibility and poor disease-free survival (DFS) of thyroid carcinoma. In addition, we also found a close association between RASSF1A promoter methylation and patient tumor stage and age, but not in patients of different genders.

Conclusions:

The methylation status of RASSF1A promoter is strongly associated with thyroid carcinoma susceptibility and DFS. The RASSF1A promoter methylation test can be applied in the clinical diagnosis of thyroid carcinoma.

Insights

Ras association domain family 1A (RASSF1A) promoter methylation is linked to increased thyroid cancer risk and poorer survival. This finding supports its potential use in clinical diagnosis for thyroid carcinoma.

Area of Science:

Oncology
Molecular Biology
Epigenetics

Background:

DNA promoter methylation, a key epigenetic mechanism, influences gene expression and cellular functions.
Ras association domain family 1A (RASSF1A) plays a critical role in biological processes, with its promoter methylation being a focus of research.
Previous studies on RASSF1A promoter methylation in thyroid carcinoma yielded conflicting results, necessitating a comprehensive analysis.

Purpose of the Study:

To investigate the association between Ras association domain family 1A (RASSF1A) promoter methylation and thyroid carcinoma susceptibility.
To explore the relationship between RASSF1A promoter methylation and thyroid carcinoma clinical characteristics, prognosis, and survival.
To clarify the conflicting findings regarding RASSF1A promoter methylation in thyroid carcinoma through meta-analysis and database mining.

Main Methods:

Meta-analysis of 14 cancer-normal studies and Gene Expression Omnibus (GEO) database data for thyroid carcinoma susceptibility.
Analysis of Cancer Genome Atlas (TCGA) project data to assess RASSF1A promoter methylation in relation to thyroid carcinoma susceptibility, clinical features, and prognosis.
Estimation of odds ratios for susceptibility and hazard ratios for prognosis, with heterogeneity assessment using I² and meta-regression.

Main Results:

Meta-analysis revealed a significant association between RASSF1A promoter methylation and increased thyroid carcinoma susceptibility with low heterogeneity.
GEO database analysis corroborated the link between RASSF1A promoter methylation and thyroid carcinoma susceptibility.
TCGA data indicated that RASSF1A promoter methylation correlates with thyroid carcinoma susceptibility, poorer disease-free survival (DFS), advanced tumor stage, and patient age.

Conclusions:

RASSF1A promoter methylation is a significant biomarker for thyroid carcinoma susceptibility and prognosis, impacting disease-free survival.
The methylation status of the RASSF1A promoter demonstrates a strong correlation with key clinical indicators such as tumor stage and patient age.
RASSF1A promoter methylation testing holds promise as a valuable tool for the clinical diagnosis and management of thyroid carcinoma.

Read full analysis

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