HYPERMETHYLATION OF p14ARF PROMOTER REGION AND EXPRESION OF p14ARF GENE PRODUCT IN NON-SMALL CELL LUNG CANCER

Objective: This study was designed to investigate promoter methylation status and protein expression of p14ARF gene in non-small cell lung cancer, and value the role of p14ARF promoter methylation in carcinogenesis of non-small cell lung cancer. Methods: Promoter methylation status and protein expression of p14ARF gene in 40 cases of non-small cell lung cancer were analyzed by methylation specific polymerase china reaction (MSP), restriction enzyme-related polymerase chain reaction (RE-PCR) and immunohistochemistry (IHC). Results: The positive rates of p14ARF promoter methylation in tumor tissues and normal tissues adjacent to cancer were 17.5% (7/40) and 2.5% (1/40) respectively. There were statistically significant differences between them, P<0.05. The results of RE-PCR were consistent with that of MSP. The expression rate of p14ARF protein in tumor tissues was significantly lower than that in normal tissues adjacent to cancer, p<0.01. Promoter methylation status and protein expression of p14ARF gene in non-small cell lung cancer showed significantly an inverse correlation (r=-0.56, P<0.01), and both of them did not relate statistically with the clinicopathologic characteristics of patients such as histological classification, clinical stage, differentiation grade and lymph node involvement. Conclusion: Promoter methylation is a crucial mechanism of inactivation of p14ARF gene. Promoter methylation of p14ARF gene might be involved in carcinogenesis of non-small cell lung cancer, and is an early event in development process of non-small cell lung cancer. It might be used as a new target in gene treatments in the future.