Evaluating the expression and methylation of CDKN2A and CDK-4 and CDK-6 expression as its targets in tumoral and marginal tissues of Lung cancer patients

Abstract

Lung cancer is one of the most common malignancies worldwide. One of the most significant changes in various cancers, especially lung cancer, is the change in cell cycle settings, so that in cancer cells, this cycle is out of control and leads to the rapid division of cancer cells. CDK-4 and CDK-6 are two major regulators of the cell cycle. These two oncogenes are among the important targets of the CDKN2A gene and the relationship between them determines the fate of the cell in the growth process. It seems that the changes in the expression and methylation of CDKN2A are related to the changes in the expression of CDK-4 and CDK-6. In this regard, in the present study, the changes in the expression level of CDK-4 and CDK-6 genes in the tissue samples of patients with lung cancer and their relationship with the level of CDKN2A gene expression and methylation were examined. Method: In this study, 50 patients with lung cancer were included in the study with informed consent. Changes in the expression of CDK-4 and CDK-6 genes were investigated by Real Time PCR method. To check the methylation level of the CDKN2A gene, the DNA of the samples was first extracted, and after extraction, it was treated with a special methylation kit and the methylation level of the desired region was evaluated by the msHRM method. Pvalue<0.05 was considered significant in statistical tests.

Result: Regarding the expression, the expression changes of all three investigated genes in tumor samples were significant with healthy samples. Meanwhile, CDK-4 and CDK-6 had increased expression and CDKN2A had decreased expression in tumor samples. On the other hand, the level of CDKN2A gene methylation in tumor samples was higher than in healthy samples, which can be a reason for its expression changes. In addition, according to the findings of our review, changes are related to some clinicopathological indicators of patients, including metastasis to lymph nodes, distant metastasis, and stage of the disease.