Gene Signatures and Prognostic Value of m6A RNA Methylation Regulators in Uterine Corpus Endometrial Carcinoma.

IF 2.1 4区 医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Discovery medicine Pub Date : 2021-05-01
Yuanling Feng, Chunfang Yao, Jiayu Shen, Jianwei Zhou
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引用次数: 0

Abstract

Background: Uterine corpus endometrial carcinoma (UCEC) is the second most common malignancy of female reproductive system. Though most UCEC are diagnosed at an early age, the mortality has increased. It is important to develop new targets for prognosis evaluation and treatment.

Methods: Expression profiles of 19 m6A regulators and UCEC samples' epidemiologic information were obtained from GTEx and TCGA datasets. Nonnegative matrix factorization (NMF) was used to cluster UCEC samples into three groups and overall survival (OS) was compared among them. Multivariate cox proportional hazard model was used to select targets for the construction of m6A-related prognosis prediction signature. A nomogram consisting of m6A-related signature, stage, and histology was provided for clinical application.

Results: Eighteen m6A regulators were found to be differentially expressed between normal sample and UCEC samples. There was a significant difference in the OS probability among three clusters with different expression levels of m6A. VIRMA, YTHDF3, and IGF2BP1 were picked as UCEC prognosis prediction signatures and the prognostic value was confirmed. Risk score estimated by this signature was demonstrated to be the independent prognostic factor for UCEC.

Conclusion: Aberrant expression of m6A RNA methylation regulators was significantly associated with the development and prognosis of UCEC. A three-gene signature consisting of VIRMA, YTHDF3, and IGF2BP1 may effectively predict the prognosis of UCEC patients.

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m6A RNA甲基化调控因子在子宫内膜癌中的基因特征及预后价值。
背景:子宫体子宫内膜癌是女性生殖系统第二常见的恶性肿瘤。尽管大多数UCEC在早期就被诊断出来,但死亡率却有所上升。寻找新的预后评价和治疗靶点具有重要意义。方法:从GTEx和TCGA数据库获取19个m6A调控因子的表达谱和UCEC样本的流行病学信息。采用非负矩阵分解法(NMF)将UCEC样本分为三组,并比较各组的总生存期(OS)。采用多变量cox比例风险模型选择构建m6a相关预后预测信号的靶点。由m6a相关特征、分期和组织学组成的nomogram图供临床应用。结果:发现18个m6A调节因子在正常样品和UCEC样品中存在差异表达。在m6A表达水平不同的3个集群中,OS概率有显著差异。选择VIRMA、YTHDF3、IGF2BP1作为UCEC的预后预测特征,确认其预后价值。通过该特征估计的风险评分被证明是UCEC的独立预后因素。结论:m6A RNA甲基化调控因子的异常表达与UCEC的发展和预后有显著关系。由VIRMA、YTHDF3和IGF2BP1组成的三基因标记可以有效预测UCEC患者的预后。
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来源期刊
Discovery medicine
Discovery medicine MEDICINE, RESEARCH & EXPERIMENTAL-
CiteScore
5.40
自引率
0.00%
发文量
80
审稿时长
6-12 weeks
期刊介绍: Discovery Medicine publishes novel, provocative ideas and research findings that challenge conventional notions about disease mechanisms, diagnosis, treatment, or any of the life sciences subjects. It publishes cutting-edge, reliable, and authoritative information in all branches of life sciences but primarily in the following areas: Novel therapies and diagnostics (approved or experimental); innovative ideas, research technologies, and translational research that will give rise to the next generation of new drugs and therapies; breakthrough understanding of mechanism of disease, biology, and physiology; and commercialization of biomedical discoveries pertaining to the development of new drugs, therapies, medical devices, and research technology.
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