Reduced promoter methylation of MYD88 and ASC/TMS1 genes in tumor tissue of patients with lung carcinoma

In lung cancer, DNA methylation has been associated with chronic inflammation and it is well known that chronic inflammation may contribute to cancer initiation, progression and dissemination. In this study we aimed to evaluate methylation status of promoter regions of two genes involved in regulation of innate immune response, ASC/TMS1 and MyD88. ASC/TMS1 is critical adaptor molecule in inflammasome activation while MyD88 is critical adaptor molecule in Toll-like receptor signaling. We tested if expression of MyD88 and ASC/TMS1 genes in tumor and healthy tissues are epigenetically regulated, by correlating protein expression levels and methylation status. We found that overall mean methylation of tested promoters is significantly hypomethylated in tumor tissues and this status is in correlation with protein expression ; MyD88 and ASC/TMS1 are expressed at higher level in tumor tissues. We also noticed tumor- specific cytokine profile on mRNA level: up regulation of cytokines such as IL-18 and IL-1β and down-regulation of cytokines such as IL- 12A, IL33 and IL-6. Association analysis indicates that hypomethylated tumor tissues at CpG4 site in ASC/TMS1 promoter are associated with decreased overall survival, and higher methylation at CpG8 in ASC/TMS1 promoter of tumor tissue is associated with TNM grade 2. Methylation status of CpGs tested in MyD88 promoter region was shown not to be associated with OS of NSCLC patients, and no such association was found for TNM grade either.