Characterization of Modification Patterns, Biological Function, Clinical Implication, and Immune Microenvironment Association of m6A Regulators in Pancreatic Cancer

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

Automated summary

The study identified genetic mutations and dysregulation in m(6)A regulators in pancreatic cancer, leading to different prognosis, immune cell infiltration, and biological functions. A m(6)A scoring system was developed to show that high m(6)A scores are associated with poor clinical outcomes and more frequent mutations. Additionally, the study found that the m(6)A scores may be useful in predicting the response to immunotherapy.