Genes associated with N6‐methyladenosine regulators provide insight into the prognosis and immune response to renal clear cell carcinoma

• Published in: Environmental toxicology Vol. 39; no. 2; pp. 626 - 642
• Main Authors: Fan, Guobin, Wu, Dejun, Chen, Huaping, Wen, Zhi, Liao, Linhui, He, Shuming, Yang, Jie
• Format: Journal Article
• Language: English
• Published: Hoboken, USA John Wiley & Sons, Inc 01.02.2024; Wiley Subscription Services, Inc
• Subjects: Animals; Cancer; Carcinoma, Renal Cell - genetics; Cell proliferation; Chemotherapy; Clear cell-type renal cell carcinoma; Clients; Clusters; cox regression; Defence mechanisms; Gender; Genes; Histopathology; Humans; Immune response; Immune system; Immunity; Kidney Neoplasms - genetics; kidney renal clear cell carcinoma (KIRC); Mice; Microenvironments; N6-methyladenosine; N6‐methyladenosine (m6A); Neoplasms; Nucleic acids; prognosis model; Proliferation; Regression analysis; Ribonucleic acid; Risk assessment; Risk groups; RNA; RNA modification; Tumor Microenvironment; N6-methyladenosine (m6A); cox regression; kidney renal clear cell carcinoma (KIRC); prognosis model
• ISSN: 1520-4081; 1522-7278
• DOI: 10.1002/tox.23920

As one of the most common messenger ribonucleic acid modifications in eukaryotic organisms, N6‐methyladenosine (m6A) is involved in a wide variety of biological functions. The imbalance of m6A RNA modification may be linked to cancer and other disorders, according to a growing body of studies. Its effects on clear cell renal cell carcinoma (KIRC) have not been well discussed, though. Here, we acquired the expression patterns of 23 important regulators of m6A RNA modification and assess how they might fare in KIRC. We observed that 17 major m6A RNA modification regulatory factors had a substantial predictive influence on KIRC. Using the “ConsensusCluster” program, we defined two groupings (Cluster 1 and Cluster 2) depending on the expression of the aforementioned 17 key m6A RNA methylation regulators. The Cluster 2 has a less favorable outcome and is strongly related with a lesser immune microenvironment, according to the findings. We also developed a strong risk profile for three m6A RNA modifiers (METTL14, YTHDF1, and LRPPRC) using multivariate Cox regression analysis. According to further research, the aforementioned risk profile could serve as an independent predicting factor for KIRC, and the chemotherapy response sensitivity was analyzed between two risk groups. Moreover, to effectively forecast the future outlook of KIRC clients, we established a novel prognostic approach according to gender, age, histopathological level, clinical stage, and risk score. Finally, the function of hub gene METTL14 was validated by cell proliferation and subcutaneous graft tumor in mice. In conclusion, we discovered that m6A RNA modifiers play an important role in controlling KIRC and created a viable risk profile as a marker of prediction for KIRC clients.