Assessment of the Prognostic Value of Methylation Status and Expression Levels of FHIT, GSTP1 and p16 in Non-Small Cell Lung Cancer in Egyptian Patients

Background: Methylation of tumor suppressor genes has been investigated in all kinds of cancer. Tumorspecific epigenetic alterations can be used as a molecular markers of malignancy, which can lead to betterdiagnosis, prognosis and therapy. Therefore, the aim of this study was to evaluate the association between genehypermethylation and expression of fragile histidine triad (FHIT), glutathione S-transferase P1 (GSTP1) andp16 genes and various clinicopathologic characteristics in primary non-small cell lung carcinomas (NSCLC).Materials and
Methods: The study included 28 primary non-small cell lung carcinomas, where an additional28 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 ofFHIT, GSTP1 and p16 while their mRNA expression levels were measured using a real-time PCR assay withSYBR Green I.
Results: The methylation frequencies of the genes tested in NSCLC specimens were 53.6% forFHIT, 25% for GSTP1, and 0% for p16, and the risk of FHIT hypermethylation increased among patientswith NSCLC by 2.88, while the risk of GSTP1 hypermethylation increased by 2.33. Hypermethylation of FHITgene showed a highly significant correlation with pathologic stage (p<0.01) and a significant correlation withsmoking habit and FHIT mRNA expression level (p<0.05). In contrast, no correlation was observed between themethylation of GSTP1 or p16 and smoking habit or any other parameter investigated (p>0.05).
Conclusions:Results of the present study suggest that methylation of FHIT is a useful biomarker of biologically aggressivedisease in patients with NSCLC. FHIT methylation may play a role in lung cancer later metastatic stages whileGSTP1 methylation may rather play a role in the early pathogenesis.