Identification of DLC-1 expression and methylation status in patients with non-small-cell lung cancer.

In order to determine whether the deleted in liver cancer-1 (DLC-1) gene is deregulated in non-small-cell lung carcinoma (NSCLC) and to assess the contribution of molecular alterations in DLC-1 to lung carcinogenesis, a total of 84 tissue specimens (30 NSCLC and 30 corresponding adjacent normal tissues; 5 benign tumor and 5 corresponding adjacent normal tissues; and 10 pulmonary bullae and 4 corresponding adjacent normal tissues), were obtained from 45 patients who underwent curative surgical resection. DLC-1 mRNA expression was evaluated by reverse transcription-quantitative polymerase chain reaction (PCR) and its protein level was assessed by western blot analysis. A significant downregulation of DCL-1 at the mRNA and protein levels was observed in NSCLC tissues when compared to benign lung tumors and normal lung tissues (P<0.001). To further determine whether the decreased expression of DLC-1 at the mRNA and protein levels is associated with the methylation of its promoter, methylation-specific PCR was performed following extraction of genomic DNA from the samples. DLC-1 promoter methylation was identified in 7 of the 30 (23.3%) NSCLC tissue samples, but not in the corresponding adjacent normal tissues from NSCLC patients or in lung tissues from non-NSCLC patients. Our data indicated that DLC-1 hypermethylation may play a crucial role in lung carcinogenesis and may be a target for the treatment of NSCLC.