Aberrant OCIAD2 demethylation in lung adenocarcinoma is associated with outcome.

Abstract

Overexpression of OCIAD2 in lung adenocarcinoma has already been reported in several research articles, but the molecular mechanism involved remains unknown. Promoter CpG methylation is a representative form of epigenetic gene regulation, and a considerable number of tumor suppressor genes show hypermethylation in many cancers. In contrast, promoter CpG hypomethylation causes oncogene overexpression, resulting in carcinogenesis and malignant progression. In the present study, we investigated the CpG methylation and expression status of OCIAD2 using tumor tissues and adjacent normal tissues from seven cases of lung adenocarcinoma. We also examined the relationship between CpG methylation status and outcome in 58 patients with adenocarcinoma. Pyrosequencing showed that CpG sites in OCIAD2 promoter regions were more frequently demethylated in tumor tissues than in adjacent normal tissues, and reverse transcription-quantitative polymerase chain reaction revealed overexpression of OCIAD2 in lung adenocarcinoma. There was a correlation between OCIAD2 CpG demethylation and the level of mRNA expression, and statistical analysis showed that CpG hypomethylation of OCIAD2 was associated with poor outcomes. Our results suggest that overexpression of OCIAD2 might be caused mainly by CpG hypomethylation and that OCIAD2 methylation status might be a useful prognostic indicator in lung adenocarcinoma.