Abstract
Methylation of tumor suppressor genes has been investigated in all kinds of cancer. Tumor specific epigenetic alterations can be used as a molecular markers of malignancy, which can lead to better diagnosis, prognosis and therapy. Therefore, the aim of this study was to evaluate the association between gene hypermethylation and expression of fragile histidine triad (FHIT), glutathione S-transferase P1 (GSTP1) and p16 genes and various clinicopathologic characteristics in primary non-small cell lung carcinomas (NSCLC). The study included 28 primary non-small cell lung carcinomas, where an additional 28 tissue samples taken from apparently normal safety margin surrounding the tumors served as controls. Methylation-specific polymerase chain reaction (MSP) was performed to analyze the methylation status of FHIT, GSTP1 and p16 while their mRNA expression levels were measured using a real-time PCR assay with SYBR Green I. The methylation frequencies of the genes tested in NSCLC specimens were 53.6% for FHIT, 25% for GSTP1, and 0% for p16, and the risk of FHIT hypermethylation increased among patients with NSCLC by 2.88, while the risk of GSTP1 hypermethylation increased by 2.33. Hypermethylation of FHIT gene showed a highly significant correlation with pathologic stage (p<0.01) and a significant correlation with smoking habit and FHIT mRNA expression level (p<0.05). In contrast, no correlation was observed between the methylation of GSTP1 or p16 and smoking habit or any other parameter investigated (p>0.05). RESULTS of the present study suggest that methylation of FHIT is a useful biomarker of biologically aggressive disease in patients with NSCLC. FHIT methylation may play a role in lung cancer later metastatic stages while GSTP1 methylation may rather play a role in the early pathogenesis.
Highlights
Lung cancer is one of the most common malignances, of which the occurrence and mortality is increasing every year due to air pollution, environmental breakdown and cigarette abuse (Xie et al, 2014)
The methylation frequencies of the genes tested in non-small cell lung carcinomas (NSCLC) specimens were 53.6% for fragile histidine triad (FHIT), 25% for glutathione S-transferase P1 (GSTP1), and 0% for p16, and the risk of FHIT hypermethylation increased among patients with NSCLC by 2.88, while the risk of GSTP1 hypermethylation increased by 2.33
Gene promoter methylation profile The frequencies of FHIT, GSTP1 and p16 promoter methylation among NSCLC and control patient groups are
Summary
Lung cancer is one of the most common malignances, of which the occurrence and mortality is increasing every year due to air pollution, environmental breakdown and cigarette abuse (Xie et al, 2014). Lung cancer can be classified into two major groups: small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). The latter group is further subdivided into squamous cell carcinoma, large cell carcinoma and adenocarcinoma.  Epigenetic silencing of genes plays an important role in the inactivation of tumor suppressor genes in carcinogenesis. Three tumor suppressor genes were chosen for assessment of their roles in lung carcinogenesis: FHIT, GSTP1 and p16 genes (Sinha et al, 2013). The aim of this study was to evaluate the association between gene hypermethylation and expression of fragile histidine triad (FHIT), glutathione S-transferase P1 (GSTP1) and p16 genes and various clinicopathologic characteristics in primary non-small cell lung carcinomas (NSCLC). FHIT methylation may play a role in lung cancer later metastatic stages while GSTP1 methylation may rather play a role in the early pathogenesis
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