Prognostic Value of m6A RNA Methylation Modulators and Potential Clinical Application in Pancreatic Cancer

Abstract Background m6A is the most prevalent and abundant form of mRNA modification and plays a dual role in cancer development. The high incidence and mortality of pancreatic cancer are critical obstacles worldwide. In this study, we investigated the function of m6A RNA methylation modulators in pancreatic cancer. Methods Expression of 13 m6A RNA methylation modulators and clinical data from patients with pancreatic adenocarcinoma were obtained from TCGA database. Differences in the expression of 13 m6A RNA methylation modulators between tumour (n = 178) and healthy (n = 4) samples were compared by Wilcoxon test. LASSO Cox regression was used to select m6A RNA methylation modulators for analysis of the relationship between expression and clinical characteristics by univariate and multivariate regression. The pathways of the m6A RNA methylation modulators were examined by gene set enrichment analysis (GSEA) and we found enrichment in chemokine, ribosome, and mTOR signalling pathways. Results WTAP had a low expression in tumour samples compared with healthy samples. Furthermore, our analyses revealed that the m6A RNA methylation modulators YTHDF1, ALKBH5, METTL3, METTL14, and KIAA1429 correlated with high-risk patients, resulting in an elevated risk score and a lower overall survival. High-risk score correlated with clinical characteristic and was an independent prognostic indicator for pancreatic adenocarcinoma. The pathways involved were identified by GSEA to explore the potential mechanism of action. Conclusion Modulators involved in m6A RNA methylation were associated with the development of pancreatic cancer. A risk score based on the expression of YTHDF1, ALKBH5, METTL3, METTL14, and KIAA1429 may be an independent prognostic indicator.