Xu Jiaju, Liu Yuenan, Liu Jingchong, Xu Tianbo, Cheng Gong, Shou Yi, Tong Junwei, Liu Lilong, Zhou Lijie, Xiao Wen, Xiong Zhiyong, Yuan Changfei, Chen Zhixian, Liu Di, Yang Hongmei, Liang Huageng, Chen Ke, Zhang Xiaoping
Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Department of Pathogenic Biology, School of Basic Medicine, Huazhong University of Science and Technology, Wuhan, China.
Front Genet. 2020 Dec 4;11:602485. doi: 10.3389/fgene.2020.602485. eCollection 2020.
RNA methylation accounts for over 60% of all RNA modifications, and N-methyladenosine (mA) is the most common modification on mRNA and lncRNA of human beings. It has been found that mA modification occurs in microRNA, circRNA, rRNA, and tRNA, etc. The mA modification plays an important role in regulating gene expression, and the abnormality of its regulatory mechanism refers to many human diseases, including cancers. Pitifully, as it stands there is a serious lack of knowledge of the extent to which the expression and function of mA RNA methylation can influence prostate cancer (PC). Herein, we systematically analyzed the expression levels of 35 mA RNA methylation regulators mentioned in literatures among prostate adenocarcinoma patients in the Cancer Genome Atlas (TCGA), finding that most of them expressed differently between cancer tissues and normal tissues with the significance of < 0.05. Utilizing consensus clustering, we divided PC patients into two subgroups based on the differentially expressed mA RNA methylation regulators with significantly different clinical outcomes. To appraise the discrepancy in total transcriptome between subgroups, the functional enrichment analysis was conducted for differential signaling pathways and cellular processes. Next, we selected five critical genes by the criteria that the regulators had a significant impact on prognosis of PC patients from TCGA through the last absolute shrinkage and selection operator (LASSO) Cox regression and obtained a risk score by weighted summation for prognosis prediction. The survival analysis curve and receiver operating characteristic (ROC) curve showed that this signature could excellently predict the prognosis of PC patients. The univariate and multivariate Cox regression analyses proved the independent prognostic value of the signature. In summary, our effort revealed the significance of mA RNA methylation regulators in prostate cancer and determined a mA gene expression classifier that well predicted the prognosis of prostate cancer.
RNA甲基化占所有RNA修饰的60%以上，而N-甲基腺苷（mA）是人类mRNA和lncRNA中最常见的修饰。现已发现，mA修饰存在于微小RNA、环状RNA、核糖体RNA和转运RNA等中。mA修饰在调节基因表达中起重要作用，其调节机制异常与包括癌症在内的多种人类疾病相关。遗憾的是，目前对于mA RNA甲基化的表达和功能在多大程度上影响前列腺癌（PC），我们仍知之甚少。在此，我们系统分析了癌症基因组图谱（TCGA）中前列腺腺癌患者文献中提及的35种mA RNA甲基化调节因子的表达水平，发现其中大多数在癌组织和正常组织之间存在差异表达，差异具有统计学意义（P<0.05）。利用一致性聚类，我们根据差异表达的mA RNA甲基化调节因子将PC患者分为两个亚组，这两个亚组具有显著不同的临床结局。为了评估亚组间全转录组的差异，我们对差异信号通路和细胞过程进行了功能富集分析。接下来，我们通过LASSO Cox回归从TCGA中筛选出对PC患者预后有显著影响的调节因子，挑选出5个关键基因，并通过加权求和获得一个风险评分用于预后预测。生存分析曲线和受试者工作特征（ROC）曲线表明，该特征能够很好地预测PC患者的预后。单因素和多因素Cox回归分析证明了该特征具有独立的预后价值。总之，我们的研究揭示了mA RNA甲基化调节因子在前列腺癌中的重要性，并确定了一个能很好预测前列腺癌预后的mA基因表达分类器。
Zotero 插件
