Assessment of Circulating Cell Free DNA Methylation Biomarker of Panel of Selected Genes for Lung Cancer Detection

Lung cancer (LC) is a well-known cause of cancer-related death worldwide. Early diagnosis of LC is an unmet need to improve the treatment response. In present study, we have analyzed the promoter methylation of a panel of genes in LC tissue and established tissue mirror biomarkers in plasma-derived circulating cell-free DNA (cfDNA). The mRNA expression of panel of genes (CDH1, CHFR, SOX10, and CAV1) were analyzed in tumor tissue (TT) including Non-Small Cell Lung Cancer (NSCLC), and Small Cell Lung Cancer (SCLC) as compared to tumor-free tissue (TF) and correlated with gene promoter methylation in tissue-derived gDNA using methylation-specific PCR. The methylation analysis of genes were further analyzed in plasma-derived cfDNA of NSCLC and SCLC compared to healthy control. The methylation frequencies of CDH1, CHFR, and SOX10 were significantly higher (p < 0.05 to p < 0.001) in TT (59.45, 45.94 and 72.97%) compared to TF (21.42, 14.28 to 28.57%) respectively. Gene expressions in TT were down-regulated (p < 0.01) in contrast to TF and negatively correlated (p < 0.001) with hypermethylation, except CAV1, which showed up-regulation with hypomethylation in TT of NSCLC. The methylation status in cfDNA exploits similar results as tissue sample, exhibited significant hypermethylation (p ≤ 0.05 to p ≤ 0.001) in cfDNA of LC as compared to healthy control, and showed 58.33 to 76.47% positive predictive value and 51.47 to 66.33% negative predictive value. This study illustrated that gene promoter methylation analysis of the panel of genes in plasma samples has the potential for diagnosis of LC, and can be used as a tissue mirror biomarker.

The online version contains supplementary material available at 10.1007/s12291-024-01255-3.