Research of the alternative splicing gene RBFOX1 in esophageal squamous cell carcinoma
10.3969/j.issn.1007-3969.2015.06.001
- VernacularTitle:选择性剪接基因RBFOX1在食管鳞癌中的研究
- Author:
Jiaying DENG
;
Kuaile ZHAO
- Publication Type:Journal Article
- Keywords:
Esophageal squamous cell carcinoma;
Alternative splicing;
Methylation;
Expression;
RBFOX1
- From:
China Oncology
2015;(6):400-407
- CountryChina
- Language:Chinese
-
Abstract:
Background and purpose: Alternative splicing is an important regulation mechanism of gene expression. Aberrant alternative splicing is associated with dysregulation of the cell cycle, activation of oncogenes and inactivation of the tumor suppressor genes. Thus, it is closely correlated with the pathogenesis and progression of various tumors. DNA methylation is an important part of epigenetic phenomena. Aberrant methylation of the gene promoter can result in gene silencing. Hypermethylation of tumor suppressor genes and DNA repair genes correlates with the onset of many different cancers. Additionally, DNA methylation acts as a pivotal factor for alternative splicing. Aberrant methylation disrupts the stabilization of the alternative splicing. This study investigated the promoter methylation and expression of RNA binding protein, fox-1 homolog 1 (RBFOX1) gene in esophageal squamous cell carcinoma (ESCC), and to elucidate its role in ESCC. Methods: MassARRAY approach and RT-PCR were used respectively to examine the methylation level of RBFOX1 gene and its expression at mRNA level in tumors and corresponding adjacent normal tissues. The correlation between methylation level and clinicopathological features was analyzed. Results:RBFOX1 methylation level and mRNA expression in tumor tissues were signiifcantly lower than those in corresponding adjacent normal tissues (41.8% vs 68.3%, P<0.01). No significant correlation was observed between methylation level and clinicopathological features. The cut-off (33.6%) was calculated as the mean of the normal samples to which we applied 2.5 SD. According to the cut-off value, the object of the study was divided into two groups. The methylation level lower than the cut-off was deifned as group 1;methylation level higher than the cut-off was deifned as group 2. The 5-year overall survival rates of the two groups were 57.0%and 35.7%, respectively (P=0.06);5-year progression-free survival rates were 48.7%and 28.9%, respectively (P=0.03). However, the multivariate analysis results indicated that TNM stage was the independent factor of prognosis.Conclusion: The methylation level and mRNA expression of RBFOX1 in tumor specimens are signiifcantly lower than those in corresponding adjacent normal tissues. The methylation level of the RBFOX1 promoter is not an independent factor of prognosis.
