Molecular characterization and prognostic relevance of m6A regulators in pancreatic adenocarcinoma

Background RNA N6-methyladenine (m6A) modification played an essential role in the occurrence and development of malignant tumors. m6A modification patterns in immune response and tumor microenvironment (TME) remains an enigma. Methods 25 m6A regulators were collected, the molecular alterations and clinical relevance of which were explored. The mutation landscape of the pancreatic adenocarcinoma (PAAD) patients was explored by using TCGA data. The expression difference of the m6A regulators was identified by TCGA and HPA data. The prognosis value of the m6A regulators was measured by TCGA and ICGC data. Consensus clustering analysis was used for different m6A modification patterns identification. CIBERSORT and ESTIMATE algorithms were used to explore the landscape of TME cell infiltration. DEG analysis was used for m6A-related gene identification. m6A-score signature was established by using univariate Cox regression analysis and PCA. Results CNV amplification of m6A regulators led to up-regulated of them in tumor tissues in comparison with normal tissues. 13 of the 25 regulators showed oncogenic features. Two distinct m6A modification patterns were defined. PAAD patients in m6Acluster A occupied better survival compared to m6Acluster B. The relationships between the two m6A patterns and different types of immune infiltrating cells were further identified. A consolidated scoring system to quantify the m6A modification pattern of individual patients was established. Patients in low m6A-score group had better OS compared with these in high m6A-score group. Subsequent analysis proved that m6A methylation modification patterns was associated with response to anti-PD-L1 immunotherapy. Conclusions The molecular alterations and prognostic implications of m6A regulators were analyzed. The distinct m6A modification patterns are crucial for understanding the heterogeneity and complexity of individual tumor microenvironments (TMEs). A comprehensive assessment of m6A modification in tumors enhances our understanding of TME infiltration characteristics and facilitates more effective immunotherapy strategies.