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N6-Methyladenosine-Related RNA Signature Predicting the Prognosis of Ovarian Cancer
Recent Patents on Anti-Cancer Drug Discovery ( IF 2.8 ) Pub Date : 2021-07-31 , DOI: 10.2174/1574892816666210615164645
Jiao Jiao 1, 2 , Longyang Jiang 3 , Yang Luo 1
Affiliation  

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.



中文翻译:

N6-甲基腺苷相关的 RNA 特征预测卵巢癌的预后

背景:N6-甲基腺苷 (m6A) RNA 甲基化是真核细胞中最普遍的 mRNA 修饰。M6A mRNA 修饰几乎影响 RNA 加工的每个阶段,包括剪接、衰减、输出、翻译和表达。多项专利报道了m6A mRNA修饰在癌症诊断和治疗中的应用。在所有妇科癌症中,卵巢癌是导致死亡的主要原因。寻找用于卵巢癌早期诊断和预后的新生物标志物迫在眉睫。

目的:在目前的研究中,我们旨在评估 m6A RNA 甲基化调节因子和 m6A 相关基因,并建立一个新的卵巢癌预后基因特征面板。

方法:我们从TCGA数据库中下载了373例卵巢癌(OC)患者的突变数据、FPKM数据和相应的临床信息。我们进行了 LASSO 回归分析和多变量 cox 回归分析,以开发风险识别基因特征面板。

结果:共获得317个候选m6A RNA甲基化相关基因。最后,选择了 12 个基因(WTAP、LGR6、ZC2HC1A、SLC4A8、AP2A1、NRAS、CUX1、HDAC1、CD79A、ACE2、FLG2 和 LRFN1)来建立签名面板。我们使用 cBioPortal 数据库分析了 OC 中选定的 12 个基因的遗传改变。在 373 名患者中,368 名患者有突变。结果显示,368 例中的 137 例(37.23%)的所有查询基因都发生了改变。12 基因签名面板被确认为独立的预后指标(P = 2.29E-18,HR = 1.699,95% CI = 1.508-1.913)。

结论:我们建立了一个有效的由 12 个基因组成的 m6A 相关基因特征组,可以预测 OC 患者的预后。高风险评分表明生存不利。我们的研究为 m6A 和 OC 之间的关系提供了新的见解。该基因特征组将有助于识别预后不良的 OC 患者,并可能成为临床实践中一个有前途的预后指标。

更新日期:2021-07-31
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