Molecular and bioinformatic analysis of apoptotic tumor suppressor genes in cervical cancer
摘要
This study aims to investigate the methylation status and mRNA expression of key apoptotic genes, including death-associated protein kinase (DAPK 1), tumor necrosis factor receptor superfamily member 6 (FAS), SMAC, and tumor necrosis factor-related apoptosis-inducing ligand receptor 1 (TRAIL-R1) and its association with clinicopathological factors in cervical cancer cases. Methylation analysis was performed on 110 cervical cancer patients using qualitative methylation-specific polymerase chain reaction (MSP). Real-time PCR was used to analyze expression levels of selected genes. All samples were also analysed for the presence of high-risk HPV types (HPV 16 and 18) with specific primer. Additionally, association with clinicopathological and risk factors were evaluated. In-silico analysis was also done for further validation. The methylation status of DAPK, TRAIL R1, SMAC, and FAS was significantly different between cancer tissues and normal tissues. DAPK (0.001), FAS (0.001), and TRAIL R1 (0.02) were hypermethylated, and SMAC was found to be hypomethylated with the highest significance of < 0.0001. HPV 16 + samples were highly significant with DAPK (0.007) and FAS (0.013), and HPV 18 + samples were significant with DAPK (0.024), FAS (0.002) and TRAIL R1 (0.009). No HPV association was found with SMAC. Methylation was found to be inversely proportional to DAPK, TRAIL R1, and FAS expression. Aberrant promoter methylation of key apoptotic genes is significantly associated with cervical cancer and may contribute to its progression. Significant correlations with HPV infection and clinicopathological factors highlight their possible potential as predictive biomarkers. However, larger studies and functional validation are needed to confirm these findings and their clinical applicability.