Expression and prognostic significance of m6A‐related genes in TP53‐mutant non‐small‐cell lung cancer. Issue 1 (23rd November 2021)

• Record Type: Journal Article
• Authors: Zhao, Zhuochen; Wan, Junhu; Guo, Manman; Wang, Yangxia; Yang, Zhengwu; Zhou, Fuyou; Li, Zhuofang; Ming, Liang
• Is Part Of: Journal of clinical laboratory analysis. Volume 36:Issue 1(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2021-11-23
• Subjects: bioinformatics -- N‐6 methylation -- NSCLC -- prognostic -- TP53 mutant; Diagnosis, Laboratory -- Periodicals; Medical laboratory technology -- Periodicals; 616
• DOI: 10.1002/jcla.24118
• Languages: English
• ISSNs: 0887-8013

Abstract

Abstract: 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. Abstract : In this study, we further explored the role of m6A regulators' function in TP53‐mutant lung cancer. First, we found the m6A expression differentially between TP53‐mutant and wild‐type non‐small‐cell lung cancer (NSCLC) patients. Then, we established a risk model using multivariate regression method, and comprehensively expounded the potential role of m6A regulators in NSCLC from aspects of prognosis verification, clinical characteristics, and molecular mechanism.