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

卵巢癌 基因 N6-甲基腺苷 基因签名 癌症研究 比例危险模型 甲基化 核糖核酸 癌症 生物 肿瘤科 生物信息学 基因表达 小RNA 遗传学 医学 内科学 甲基转移酶
作者
Jiao Jiao,Longyang Jiang,Yang Luo
出处
期刊:Recent Patents on Anti-cancer Drug Discovery [Bentham Science]
卷期号:16 (3): 407-416 被引量:15
标识
DOI:10.2174/1574892816666210615164645
摘要

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.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.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.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).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.

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