Expression and Prognostic Significance of m6A-Related Genes in TP53-Mutant Non-Small-Cell Lung Cancer

作者：Zhuochen Zhao, Junhu Wan, Manman Guo, Yangxia Wang, Zhengwu Yang, Zhuofang Li, Liang Ming · 发表于：Research Square · 年份：2020 · DOI：10.21203/rs.3.rs-127631/v1 · 被引用次数：1 · 研究领域：RNA modifications and cancer、Cancer-related gene regulation、Cancer-related molecular mechanisms research

Abstract Background : TP53 is an important tumor suppressor gene on human chromosome 17. TP53 mutations have been confirmed in more than 60% of tumor patients' somatic cells. N6-methyladenosine is an enzyme that plays an important role in mRNA splicing, translation, and stabilization. It is a common internal modification of nucleotides, that is regulated by methyltransferases ("writer"), binding proteins ("reader"), and demethylases ("eraser"). However, its role in TP53 mutant non-small-cell lung cancer remains unknown. In this study, we investigated 17 common N-6-Methyladenosine regulators' contributions and prognostic values. Results : Wilcox test showed that 9 of 17 m6A regulators were expressed differently between TP53 mutant and wild type NSCLC (p<0.05). A new way of tumor typing is attempted by consensus clustering. Using univariate cox regression analysis, ALKBH5, HNRNPA2B1 were associated with the prognostic of TP53 mutant patients. Then we built signatures of N-6-Methyladenosine regulators with prognostic ability based on the multivariate cox regression in TP53 mutant cohorts. Moreover, ROC curve showed that this signature could predict the prognostic in mutant cohort well and the riskscore for patients was calculated. With this riskscore, patients with TP53 mutations can be divided into high and low risk groups, and there was a significant difference between two groups. Finally, we found 338 DEGs between high and low risk groups, then GO enrichment analysis, PPI ...