A Newly Defined Risk Signature, Consisting of Three m <sup>6</sup>A RNA Methylation Regulators, Predicts the Prognosis of Ovarian Cancer

Abstract

N6-methyladenosine (m6A) RNA methylation, involved in cancer initiation and progression, is dynamically regulated by the m6A RNA methylation regulators, including ‘writers’, ‘erasers’ and ‘readers’. However, the expression of m6A RNA methylation regulators in ovarian cancer and their correlation with prognosis remain elusive. Here, we demonstrated that the 18 central m6A RNA methylation regulators were expressed differently between ovarian cancer (OC) and normal tissues, and can be divided into two categories according to their enrichment in tumor vs normal tissues. Additionally, by applying consensus clustering, all OC patients cases can be divided into three subgroups (cluster1/2/3) based on expression levels of all 18 m6A RNA methylation regulators. Moreover, we systematically analyzed the prognostic value of 18 m6A RNA methylation regulators in OC and found that IGF2BP1, VIRMA, and ZC3H13 yield the highest scores for predicting the prognosis of OC. Therefore, we derived a risk signature consisting of these three selected m6A RNA methylation regulators as an independent prognostic marker for OC and validated our findings with data derived from a different OC cohort. Moreover, by the Gene Set Enrichment Analysis (GSEA), we demonstrated that the three selected regulators were all correlated with pathways in cancer and WNT signaling pathways. In conclusion, m6A methylation regulators are vital participants in OC, and IGF2BP1, VIRMA, and ZC3H13 are valuable for prognosis prediction and treatment strategy development. Funding Statement: Contributions were made by the TCGA network, the GTEx network and the CCLE Network. This study was supported by grants from the National Natural Science Foundation of China (No. 81572900). The National Key R&D Program of China, Stem Cell and Translation Research (No. 2016YFA0102000). The Fundamental Research Funds for the Central Universities of Central South University (No. 502221804). Declaration of Interests: The authors declare that they have no competing interests. Ethics Approval Statement: Not required.