The epigenetic inactivation of tumor suppressor genes may play an important role in the development and progression of many
cancer types, including
lung cancer. Therefore, we investigated the association between the aberrant promoter methylation of 2 genes: the
Death-Associated Protein Kinase (DAPK) and the Ras Association Domain Family 1A (RASSF1A) by using methylation-specific PCR, and the clinicopathological features and prognosis in 70 radically resected non-small cell
lung cancers (NSCLCs). Hypermethylation of the DAPK and RASSF1A promoters was found in 24 (34%), and in 18 (26%)
tumor DNA samples, respectively. Regarding different clinicopathological features of NSCLCs, the DAPK promoter methylation was more frequently observed in
squamous cell carcinoma (46%) than in
adenocarcinoma (25%) and
large cell carcinoma (22%), but there were no significant statistical differences (p=0.3). On the other hand, a statistically significant trend was observed between the RASSF1A methylation and a histological type of
tumor (p=0.06). 45% of
adenocarcinoma tumors showed RASSF1A promoter methylation in comparison to 17% of
squamous cell carcinomas and 22% of
large cell carcinomas. When both markers were analyzed according to the
tumor-node-
metastasis (TNM) staging system, no statistically significant differences were observed between stage I, II and IIIa, and the DAPK (p=0.2) and RASSF1A methylation (p=0.1). In comparison, when stage I and II were grouped together and considered vs. stage IIIa, a significant association between RASSF1A methylation and the TNM was found (p=0.03). The group of patients with
tumors showing DAPK promoter methylation had significantly poorer overall survival rates (p=0.02) than the patients with
tumors that did not show DAPK promoter methylation. However, the association between the RASSF1A promoter methylation status and the overall survival rates was not statistically significant (p=0.48). In conclusion, this paper supports the importance of epigenetic gene regulation in
lung cancer progression and prognosis.