DNA methylation profiling identifies the HOXA11 gene as an early diagnostic and prognostic molecular marker in human lung adenocarcinoma

Abstract

DNA hypermethylation plays important roles in carcinogenesis by silencing key genes. The goal of our study was to identify pivotal genes using MethyLight and assessed their diagnostic and prognostic values in lung adenocarcinoma (AD). In the present study, we detected DNA methylation at sixteen loci promoter regions in twenty one pairs of primary human lung AD tissues and adjacent non-tumor lung (AdjNL) tissues using the real-time PCR (RT-PCR)-based method MethyLight. By comparing the sixteen analyzed loci in lung AD tissues and AdjNL and non-tumor (NL) tissues, we found that, among the six genes identified with hypermethylation, the HOXA11, CDKN2A-EX2 and EYA4 genes showed highly promising DNA hypermethylation diagnostic markers in the lung AD tissues. Moreover, comparing lung AD tissues (> 2 cm in diameter) to the AdjNL or AD in situ (AIS) tissues by RT-qPCR and immunohistochemistry revealed that HOXA11 expression was significantly increased. A further study showed that HOXA11 expression was controlled by methylation in the promoter region in human lung tumor cell lines. Aberrant hypermethylation and the methylation-induced down-regulation of HOXA11 may promote tumor progression. Our results suggested that HOXA11 might be a diagnostic and prognostic marker in patients with lung AD.