N6-Methyladenosine-Related RNA Signature Predicting the Prognosis of Ovarian Cancer

Abstract

Background: N6-Methyladenosine (m6A) RNA methylation is the most universal mRNA modification in eukaryotic cells. M6A mRNA modification affects almost every phases of RNA processing, including splicing, decay, export, translation and expression. Several patents have reported the application of m6A mRNA modification in cancer diagnosis and treatment. Ovarian cancer is the leading cause of death among all gynecological cancers. It is urgent to identify new biomarkers for early diagnosis and prognosis of ovarian cancer. Objective: In the current study, we aimed to evaluate the m6A RNA methylation regulators and m6A related genes and establish a new gene signature panel for the prognosis of ovarian cancer. Methods: We downloaded the mutations data, FPKM data and corresponding clinical information of 373 patients with Ovarian Cancer (OC) from the TCGA database. We performed LASSO regression analysis and multivariate cox regression analysis to develop a risk-identifying gene signature panel. Results: A total of 317 candidate m6A RNA methylation related genes were obtained. Finally, 12 - genes (WTAP, LGR6, ZC2HC1A, SLC4A8, AP2A1, NRAS, CUX1, HDAC1, CD79A, ACE2, FLG2 and LRFN1) were selected to establish the signature panel. We analyzed the genetic alterations of the selected 12 -genes in OC using cBioPortal database. Among the 373 patients, 368 patients have mutations. The results showed that all queried genes were altered in 137 of 368 cases (37.23%). The 12-gene signature panel was confirmed as an independent prognostic indicator (P =2.29E-18, HR = 1.699, 95% CI = 1.508-1.913). Conclusion: We established an effective m6A-related gene signature panel consisted of 12 -genes, which can predict the outcome of patients with OC. The high risk score indicates unfavorable survival. Our study provided novel insights into the relationship between m6A and OC. This gene signature panel will be helpful in identifying poor prognostic patients with OC and could be a promising prognostic indicator in clinical practice.