Interplay of RNA m⁶A/m¹A/m⁵C/m⁷G/ψ Regulators Predicting the Prognosis of Pancreatic Cancer

N⁶-methyladenosine (m⁶A), N¹-methyladenosine (m¹A), 5-methylcytosine (m⁵C), 7-methylguanosine (m⁷G), and pseudouridine (ψ) have been identified as the most prevalent epitranscriptomic modifications on eukaryotic RNAs. It is not yet clear about the comprehensive analysis of RNA m⁶A/m¹A/m⁵C/m⁷G/ψ in pancreatic cancer, one of the most aggressive malignancies all over the whole world. We have identified that most of the RNA m⁶A/m¹A/m⁵C/m⁷G/ψ regulators are highly expressed in pancreatic cancer. Copy number variations (CNVs) or the methylation level of some genes are associated with their mRNA expression and affect the overall survival of patients. The expression of most of the regulators is positively related to the immune cell infiltration of the tumor microenvironment (TME). Furthermore, the regulators or TME-infiltrated cells are associated with tumor heterogeneity or tumor stemness. According to the similarity of TME-infiltrating cells, we classify patients into two different clusters, and we find that patients in cluster 1 (C1) are at high risk, have worse prognoses, and are more sensitive to drug treatment than cluster 2 (C2). Three machine learning algorithms, least absolute shrinkage and selection operator (LASSO), support vector machine-recursive feature elimination (SVM-RFE), and random forest (RF), show that some regulators have a strong correlation with survival. Our study has revealed the potential roles of regulators in pancreatic cancer, which may provide new insights into the field of pancreatic cancer research.