Immune-related gene methylation prognostic instrument for stratification and targeted treatment of ovarian cancer patients toward advanced 3PM approach

Background DNA methylation is an important mechanism in epigenetics, which can change the transcription ability of genes and is closely related to the pathogenesis of ovarian cancer (OC). We hypothesize that DNA methylation is significantly different in OCs compared to controls. Specific DNA methyla...

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Bibliographic Details
Published in:The EPMA journal 2024-06, Vol.15 (2), p.375-404
Main Authors: Jia, Wenshuang, Li, Na, Wang, Jingjing, Gong, Xiaoxia, Ouedraogo, Serge Yannick, Wang, Yan, Zhao, Junkai, Grech, Godfrey, Chen, Liang, Zhan, Xianquan
Format: Article
Language:English
Subjects:
Biomarkers
Biomedical and Life Sciences
Biomedicine
Cancer
Cancer therapies
Care and treatment
Comparative analysis
DNA
DNA methylation
Drug resistance
Drug therapy
Epigenetic inheritance
Genes
Genetic aspects
Genetic research
Genetic transcription
Health aspects
Medical research
Medicine, Experimental
Medicine/Public Health
Methylation
Ovarian cancer
Pathogenesis
Pharmacogenetics
Protein-protein interactions
Transferases
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Summary:Background DNA methylation is an important mechanism in epigenetics, which can change the transcription ability of genes and is closely related to the pathogenesis of ovarian cancer (OC). We hypothesize that DNA methylation is significantly different in OCs compared to controls. Specific DNA methylation status can be used as a biomarker of OC, and targeted drugs targeting these methylation patterns and DNA methyltransferase may have better therapeutic effects. Studying the key DNA methylation sites of immune-related genes (IRGs) in OC patients and studying the effects of these methylation sites on the immune microenvironment may provide a new method for further exploring the pathogenesis of OC, realizing early detection and effective monitoring of OC, identifying effective biomarkers of DNA methylation subtypes and drug targets, improving the efficacy of targeted drugs or overcoming drug resistance, and better applying it to predictive diagnosis, prevention, and personalized medicine (PPPM; 3PM) of OC. Method Hypermethylated subtypes (cluster 1) and hypomethylated subtypes (cluster 2) were established in OCs based on the abundance of different methylation sites in IRGs. The differences in immune score, immune checkpoints, immune cells, and overall survival were analyzed between different methylation subtypes in OC samples. The significant pathways, gene ontology (GO), and protein-protein interaction (PPI) network of the identified methylation sites in IRGs were enriched. In addition, the immune-related methylation signature was constructed with multiple regression analysis. A methylation site model based on IRGs was constructed and verified. Results A total of 120 IRGs with 142 differentially methylated sites (DMSs) were identified. The DMSs were clustered into a high-level methylation group (cluster 1) and a low-level methylation group (cluster 2). The significant pathways and GO analysis showed many immune-related and cancer-associated enrichments. A methylation site signature based on IRGs was constructed, including RORC|cg25112191, S100A13|cg14467840, TNF|cg04425624, RLN2|cg03679581, and IL1RL2|cg22797169. The methylation sites of all five genes showed hypomethylation in OC, and there were statistically significant differences among RORC|cg25112191, S100A13|cg14467840, and TNF|cg04425624 ( p  
ISSN:1878-5077
1878-5085
1878-5085
DOI:10.1007/s13167-024-00359-3