Genome-Wide Methylation Analysis in Two Wild-Type Non-Small Cell Lung Cancer Subgroups with Negative and High PD-L1 Expression.

Simple Summary: PD-L1 is a marker that helps determine a tumor's immune status and is used to select patients for immune therapy. Methylation modifies gene expression by adding a methyl group to DNA without affecting its sequence. In our study, we assessed and correlated PD-L1 and methylation status in pulmonary adenocarcinomas with high and negative PD-L1 expression. We investigated the pathobiological functions of the highest-ranking genes and promoters in both groups by searching genomic databases for their role in carcinomas. We observed distinct methylation patterns between PD-L1 high- and low-expressing tumors, indicating differences in their biological characteristics and tumor development. We conducted a pilot study to analyze the differential methylation status of 20 primary acinar adenocarcinomas of the lungs. These adenocarcinomas had to be wild type in mutation analysis and had either high (TPS > 50%; n = 10) or negative (TPS < 1%; n = 10) PD-L1 status to be integrated into our study. To examine the methylation of 866,895 specific sites, we utilized the Illumina Infinium EPIC bead chip array. Both hypermethylation and hypomethylation play significant roles in tumor development, progression, and metastasis. They also impact the formation of the tumor microenvironment, which plays a decisive role in tumor differentiation, epigenetics, dissemination, and immune evasion. The gained methylation patterns were correlated with PD-L1 expression. Our analysis has identified distinct methylation patterns in lung adenocarcinomas with high and negative PD-L1 expression. After analyzing the correlation between the methylation results of genes and promoters with their pathobiology, we found that tumors with high expression of PD-L1 tend to exhibit oncogenic effects through hypermethylation. On the other hand, tumors with negative PD-L1 expression show loss of their suppressor functions through hypomethylation. The suppressor functions of hypermethylated genes and promoters are ineffective compared to simultaneously activated dominant oncogenic mechanisms. The tumor microenvironment supports tumor growth in both groups. [ABSTRACT FROM AUTHOR]