SMAD4 Gene Methylation May Be Effective in Adenocarcinoma Lung Cancers

Objective: In this study, we aimed to investigate the effect of promoter region methylation of small mothers against decapentaplegic 4 (SMAD4) gene in adenoma type lung cancer cases. Adenocarcinoma and squamous type carcinomas are the most common types of lung cancer. SMAD4 gene is an intracellular signal protein. The protein of this gene, which is one of the transcription factors, functions in tissue homeostasis during embryonic development and has effects in the cancer process. Methods: In this retrospective study, a total of 40 samples including 20 paraffin-embedded tumor tissues of 20 patients with adenocarcinoma lung cancer and normal lung tissue of the same patients were included. After DNA isolation from this paraffin-embedded adenocarcinoma lung tumor tissue and its normal counterparts, methylation specific polymerase chain reaction followed by agarose gel imaging methods were applied to investigate the SMAD4 promoter methylation after bisulfite modification. Results: As a result of our study, an increased presence of methylation in the promoter region of the SMAD4 gene in the tumor tissue of a total of 12 (60%) of 20 adenocarcinoma cases compared to normal tissue was detected. A statistically significant increase in methylation rate of approximately 25-45% was found in tumor tissues of these cases compared to normal tissues (p<0.05). Conclusion: As a result of our study, we suggested that SMAD4 gene methylation may be a tumor marker for lung cancers and may contribute to the development of cancer by inhibiting SMAD4 protein expression by gene methylation and disrupting the intracellular signal pathway.