Identification of methyltransferase modification genes associated with prognosis and immune features of pancreatic adenocarcinoma

Abstract

Background: Pancreatic adenocarcinoma (PAAD) is a malignant tumor with a high mortality rate. Methylation modifications acted a crucial role to affect cancer progression. The current study aimed to explore the potential role of methylase regulators in PAAD prognosis and immune microenvironment. Methods: PubMed and TCGA databases were used to systematically analyze methylase regulators in PAAD. We identified three methylase clusters based on RNA methylase transcriptome data and obtained three gene clusters based on methylase modification-related differently expressed genes using principal component analysis (PCA) analysis. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and Gene Ontology (GO) biological processes were performed to explore the processes enriched in the different subgroups and single sample gene-set enrichment analysis (ssGSEA) was used to analyze the relationship between subgroups and immune infiltration in PAAD. Results: We systematically screened 43 methylase regulators in PAAD samples and identified three methylase clusters with different clinical outcomes, as well as detected a significant relationship between methylase clusters and tumor immune infiltration. The top ten mutated genes include TP53, Kirsten rat sarcoma viral oncogene homolog (KRAS), titin gene (TTN), mucin 16 (MUC16), SMAD4, cyclin-dependent kinase inhibitor 2a (CDKN2A), Ryanodine receptor isoform-1 (RYR1), ring finger 43 (RNF43), protocadherin-15 (PCDH15), and AT-rich interacting domain-containing protein 1 A gene (ARID1A). Conclusion: The current study constructed an m6A/m5C/m1A/m7G modulator genes and explored methylase modification-related genes, which were related to the prognosis of PAAD patients and the immune checkpoint point cytotoxic T-lymphocyte associated protein 4 (CTLA4). These findings may provide prognostic predictors and direction for immunotherapy strategies for the treatment of PAAD.