M1A regulator ALKBH1 and TRMT10B as potential prognostic bio markers and related to the tumor immune microenvironment in pan creatic adenocarcinoma

Background: N1-methyladenosine (m1A) RNA methylation is crucial in carcinogenesis and tumorous molecular pathogenesis. However, the detailed pathogenic mechanism of m1A regulators in pancreatic adenocarcinoma (PAAD) has not been comprehensively researched. Therefore, the purpose of this study was to investigate the role of m1A in PAAD prognosis and tumor microenvironment (TME). Methods The relationship between m1A regulators and the PAAD prognosis was analyzed with the cBioportal database. RNA-seq transcriptome was obtained from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases for differential expression analysis. The role of m1A regulators in the PAAD TME was analyzed wthe ith TISIDB database and R software. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichmanalysesysis were performed by The Database for Annotation, Visualization, and Integrated Discovery (DAVID). Results In PAAD, we discovered 10 m1A regulators correlated to poor prognosis and were all upregulated. While up-regulated ALKBH1 and TRMT10B were associated with a better prognosis in PAAD patients. Further research found that ALKBH1 and TRMT10B significantly upregulated the infiltrating level of immune cells, especially CD4 + T cells. Additionally, they also affected the expression of immunomodulators, including CD276, TMEM173, TNFSF9, etc. Finally, GO and KEGG enrichment analysis proved that ALKBH1 and TRMT10B influenced the PAAD development by regulating the RNA polymerase II. Conclusion Promoted expression of ALKBH1 and TRMT10B was significantly related to a better prognosis in PAAD, the possible mechanism of which might associate with the alternation of the TME. ALKBH1 and TRMT10B were potential prognosis biomarkers and possible immunotherapeutic targets for PAAD.