The methylation modification of m6A regulators contributes to the prognosis of ovarian cancer

Abstract

Background: Ovarian cancer (OV) is the leading cause of death in gynecological cancer. The dysregulation of N6-methyladenosine (m6A) modification is commonly found in cancers. However, there is a lack of research into m6A RNA methylation regulators in OV. Methods:The RNA-Seq of 379 OV tissues and 88 healthy ovarian tissues was downloaded from The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) databases, respectively. A Gene Ontology (GO) functional analysis was performed to verify the function of m6A RNA methylation regulators. Kaplan-Meier (K-M) curves and the log-rank (Mantel-Cox) test were used for the survival analysis. A Cox regression analysis was used to identify the genes related to overall survival (OS) and build the prediction model.Results: m6A RNA methylation regulators were dysregulated in OV tissues compared with normal tissues (P<0.05), and patients with a high expression of KIAA1429 and YTHDC2 had a poor prognosis (P<0.05).A prognostic model was constructed based on the m6A RNA methylation regulators. Based on the risk signature, the patients were classified into high-and low-risk groups. The low-risk group's OS rate was significantly better than that of the high-risk group. The validity and accuracy of the prognostic model were verified by using TCGA and Gene Expression Omnibus (GEO) datasets, and the risk score from the prognostic model acted as an independent prognostic indicator in predicting the survival of OV patients.Conclusions: m6A RNA methylation regulators were dysregulated in OV tissues. More importantly, the prognostic model comprising the five selected m6A RNA methylation regulators could be a valuable tool for predicting the prognosis of OV patients.

RNA epigenetic modifications in ovarian cancer: The changes, chances, and challenges

“…Studies have also shown that the other YTH members, YTHDF3, YTHDC1, and YTHDC2, have different functions and are associated with the poor prognosis of OC (Q. Wang, Zhang, et al, 2021;Zhu et al, 2022).…”

“…This indicates that the various RNA modification regulators do not function independently, and that the specific relationship between them needs further exploration. In addition, zinc finger CCCH domain‐containing protein 13 (ZC3H13), VIRMA, and methyltransferase‐like 16 (METTL16) are associated with a poor prognosis of OC (Fan et al, 2020; Zheng et al, 2021; Zhu et al, 2022). Compared with METTL3, little is known about these other m 6 A writers.…”

“…In OC tissue, the downregulation or mutation of FBW7 enhances the expression of YTHDF2, which functions as an oncogene (F. Xu, Li, et al, 2021). Studies have also shown that the other YTH members, YTHDF3, YTHDC1, and YTHDC2, have different functions and are associated with the poor prognosis of OC (Q. Wang, Zhang, et al, 2021; Zhu et al, 2022).…”

Roles of N6-methyladenosine (m6A) modifications in gynecologic cancers: mechanisms and therapeutic targeting

“…Han et al reported the correlation of genetic mutations in patients with OC with the survival and m 6 A regulator genes [ 84 ]. Zhu et al reported the association of YTHDC2 and KIAA1429 with the prognosis of OC patients [ 88 ]. In addition, researchers have established genetic models to predict the prognosis of OC patients.…”

Research Advances in the Roles of N6-Methyladenosine Modification in Ovarian Cancer

“…They constructed a prognostic model based on 5 m6A RNA methylation regulators in OC (KIAA1429, YTHDC2, ZC3H13, WTAP, and FTO) that are highly expressed in OC. 87 …”