Analyses of P16^INK4a gene promoter methylation relative to molecular, demographic and clinical parameters characteristics in non-small cell lung cancer patients: A pilot study

Abstract

Background: The aim of this study was to examine the methylation status of p16INK4a promoter region in non small cell lung cancer (NSCLC) patients and their associations with single nucleotide polymorphisms (SNPs) of the epidermal growth factor receptor (EGFR) gene, as well as with demographic or clinical characteristics. Methods: Formalin-fixed and paraffin-embedded (FFPE) DNA samples extracted from 22 NSCLC patients were analyzed with methylation-specific polymerase chain reaction (PCR) method to obtain promoter methylation profile. The same cohort was genotyped for − 216G > T, -191 C > A, and 181,946 C > T EGFR SNPs. Results: There was a significant association between methylated p16INK4a in patients prior therapy (p = 0.017) since a significantly higher frequency of methylated p16INK4a was detected in these patients (40.9%) in comparison to frequency in patients after therapy (31.8%). Also, a higher frequency of methylated p16INK4a was detected among patients with leucopenia (p = 0.056). No associations were observed between the methylation status of the p16INK4a promoter region and EGFR SNPs or other clinical and demographic data in this cohort. Conclusion: High frequency of methylation of the p16INK4a gene promoter was observed in NSCLC patients prior therapy and with leucopenia that can indicate their significance related to advanced clinical stage.