RASGRF1 Hypermethylation, a Putative Biomarker of Colorectal Cancer.

OBJECTIVE: RASGRF1 is a guanine nucleotide exchange factor, which promotes the release of GDP from inactive Ras and stabilizes the apoprotein. In this study, the methylation status of RASGRF1 promoter and its correlation with clinicopathological parameters were evaluated in colorectal cancer (CRC).

METHODS: Methylation-specific PCR and bisulfate-sequencing PCR were carried out to investigate the promoter methylation status of the RASGRF1 gene in tumor tissues and adjacent non-tumor tissues of 68 CRC patients. The effect of RASGRF1 promoter hypermethylation on its mRNA and protein expression was evaluated by quantitative reverse-transcriptase polymerase chain reaction and immunohistochemistry.

RESULTS: RASGRF1 was methylated in 58.6% tumor tissues and negatively correlated with its mRNA or protein expression. There was a statistical relationship between the degree of differentiation, lymph node metastasis and clinical stage and RASGRF1 hypermethylation. Furthermore, RASGRF1 mRNA and protein levels in tumor tissues were both significantly decreased compared with that in adjacent non-tumor tissues. In addition, the correlations between RASGRF1 hypermethylation, mRNA or protein expression, and overall survival were statistically significant.

CONCLUSIONS: Collectively, our data suggest that RASGRF1 hypermethylation is involved in an epigenetic field defect in CRC and that it might be a potential risk factor for CRC.