Zhang Qijie, Luan Jiaochen, Song Lebin, Wei Xiyi, Xia Jiadong, Song Ninghong
Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Department of Dermatology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
J Cancer. 2021 Apr 24;12(12):3575-3586. doi: 10.7150/jca.55140. eCollection 2021.
M6A RNA modification is closely associated with tumor genesis and progression of several malignancies; however, its role in prostate cancer (PCa) remains poorly understood. Expression data and corresponding clinicopathologic information were available freely from the Cancer Genome Atlas (TCGA) dataset. We compared the expression level of m6A RNA methylation regulators in PCa with different clinicopathologic characteristics and identified subgroups based on their expressions with consensus clustering. To build the signature and assess its prognostic value, several methods were used for the analysis, including univariate Cox regression analysis, Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis, time-dependent receiver operating curve (ROC), and Kaplan-Meier (KM) survival analysis. Most of the m6A RNA methylation regulators were differentially expressed not only between normal and tumor tissue but also among PCa stratified by different clinicopathologic characteristics. There were obvious differences between two clusters, cluster 1 and 2, regarding clinicopathologic features, and the recurrence-free survival (RFS) in cluster 2 was significantly worse than cluster 1. We developed an eleven-gene signature which exhibited a high prognostic value and was able to independently predict RFS. Moreover, a nomogram which integrated clinical information and the gene signature was capable of distinguishing high-risk recurrent patients. These methylation regulators are correlated to clinicopathologic characteristics in PCa and a prognostic model using m6A methylation-related genes is constructed and of high predictive value for recurrence after RP.
m6A RNA修饰与多种恶性肿瘤的发生和进展密切相关；然而，其在前列腺癌（PCa）中的作用仍知之甚少。癌症基因组图谱（TCGA）数据集可免费获取表达数据及相应的临床病理信息。我们比较了具有不同临床病理特征的PCa中m6A RNA甲基化调节因子的表达水平，并通过一致性聚类根据其表达情况确定了亚组。为构建特征并评估其预后价值，我们使用了多种分析方法，包括单变量Cox回归分析、最小绝对收缩和选择算子（LASSO）回归分析、时间依赖性受试者工作特征曲线（ROC）以及Kaplan-Meier（KM）生存分析。大多数m6A RNA甲基化调节因子不仅在正常组织和肿瘤组织之间存在差异表达，而且在按不同临床病理特征分层的PCa中也存在差异表达。在临床病理特征方面，第1组和第2组两个聚类之间存在明显差异，第2组的无复发生存期（RFS）明显比第1组差。我们开发了一个具有高预后价值且能够独立预测RFS的11基因特征。此外，一个整合了临床信息和基因特征的列线图能够区分高风险复发患者。这些甲基化调节因子与PCa的临床病理特征相关，并且构建了一个使用m6A甲基化相关基因的预后模型，该模型对根治性前列腺切除术后的复发具有较高的预测价值。
