Version 1
: Received: 28 March 2024 / Approved: 29 March 2024 / Online: 29 March 2024 (10:53:14 CET)
How to cite:
Hutarew, G.; Alinger-Scharinger, B.; Sotlar, K.; Kraus, T.F. Genome-Wide Methylation Analysis in Two Wild-Type Non-small Cell Lung Cancer Subgroups with Low and High PD-L1 Expression Levels. Preprints2024, 2024031834. https://doi.org/10.20944/preprints202403.1834.v1
Hutarew, G.; Alinger-Scharinger, B.; Sotlar, K.; Kraus, T.F. Genome-Wide Methylation Analysis in Two Wild-Type Non-small Cell Lung Cancer Subgroups with Low and High PD-L1 Expression Levels. Preprints 2024, 2024031834. https://doi.org/10.20944/preprints202403.1834.v1
Hutarew, G.; Alinger-Scharinger, B.; Sotlar, K.; Kraus, T.F. Genome-Wide Methylation Analysis in Two Wild-Type Non-small Cell Lung Cancer Subgroups with Low and High PD-L1 Expression Levels. Preprints2024, 2024031834. https://doi.org/10.20944/preprints202403.1834.v1
APA Style
Hutarew, G., Alinger-Scharinger, B., Sotlar, K., & Kraus, T.F. (2024). Genome-Wide Methylation Analysis in Two Wild-Type Non-small Cell Lung Cancer Subgroups with Low and High PD-L1 Expression Levels. Preprints. https://doi.org/10.20944/preprints202403.1834.v1
Chicago/Turabian Style
Hutarew, G., Karl Sotlar and Theo F.J. Kraus. 2024 "Genome-Wide Methylation Analysis in Two Wild-Type Non-small Cell Lung Cancer Subgroups with Low and High PD-L1 Expression Levels" Preprints. https://doi.org/10.20944/preprints202403.1834.v1
Abstract
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 low (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 low PD-L1 expression. After analyzing the correlation between 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 low 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.
Keywords
Lung cancer; Epigenetic profiling; Methylome; Methylation analysis; Programmed cell death ligand 1; Precision medicine
Subject
Medicine and Pharmacology, Pathology and Pathobiology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
