Characterization of Modification Patterns, Biological Function, Clinical Implication, and Immune Microenvironment Association of mA Regulators in Pancreatic Cancer.

N-methyladenosine (mA) modification may modulate various biological processes. Nonetheless, clinical implications of mA modification in pancreatic cancer are undefined. Herein, this study comprehensively characterized the mA modification patterns in pancreatic cancer based on mA regulators. Genetic mutation and expression pattern of 21 mA regulators and their correlations were assessed in pancreatic cancer from TCGA dataset. mA modification patterns were clustered using unsupervised clustering analysis in TCGA and ICGC datasets. Differences in survival, biological functions and immune cell infiltrations were assessed between modification patterns. A mA scoring system was developed by principal component analysis. Genetic mutations and TIDE scores were compared between high and low mA score groups. ZC3H13 (11%), RBM15B (9%), YTHDF1 (8%), and YTHDC1 (6%) frequently occurred mutations among mA regulators. Also, most of regulators were distinctly dysregulated in pancreatic cancer. There were tight crosslinks between regulators. Two mA modification patterns were constructed, with distinct prognoses, immune cell infiltration and biological functions. Furthermore, we quantified mA score in each sample. High mA scores indicated undesirable clinical outcomes. There were more frequent mutations in high mA score samples. Lower TIDE score was found in high mA score group, with AUC = 0.61, indicating that mA scores might be used for predicting the response to immunotherapy. Collectively, these data demonstrated that mA modification participates pancreatic cancer progress and ornaments immune microenvironment, providing an insight into pancreatic cancer pathogenesis and facilitating precision medicine development.