Expression and prognostic significance of m6A-related genes in TP53-mutant non-small-cell lung cancer.

Background: TP53 is an important tumor suppressor gene on human 17th chromosome with its mutations more than 60% in tumor cells. Lung cancer is the highest incidence malignancy in men around the world. N-6 methylase (m6A) is an enzyme that plays an important role in mRNA splicing, translation, and stabilization. However, its role in TP53-mutant non-small-cell lung cancer (NSCLC) remains unknown.

Method: First, we investigated 17 common m6A regulators' prognostic values in NSCLC. Then, after the establishment of risk signature, we explored the diagnostic value of m6A in TP53-mutant NSCLC. Finally, gene set enrichment analysis (GSEA), gene ontology (GO) enrichment analysis, and differential expression analysis were used to reveal the possible mechanism of m6A regulators affecting TP53-mutant NSCLC patients.

Results: Study showed that nine m6A regulators (YTHDC2, METTL14, FTO, METTL16, YTHDF1, HNRNPA2B1, RBM15, KIAA1429, and WTAP) were expressed differently between TP53-mutant and wild-type NSCLC (p < 0.05); and ALKBH5 and HNRNPA2B1 were associated with the prognostic of TP53-mutant patients. After construction of the risk signature combined ALKBH5 and HNRNPA2B1, we divided patients with TP53 mutations into high- and low-risk groups, and there was a significant survival difference between two groups. Finally, 338 differentially expression genes (DEGs) were found between high- and low-risk groups. GO enrichment analysis, PPI network, and GSEA enrichment analysis showed that m6A may affect the immune environment in extracellular and change the stability of mRNA.

Conclusion: In conclusion, m6A regulators can be used as prognostic predictors in TP53-mutant patients.