Department of Urology, The First Affiliated Hospital of Zhengzhou University, China.
Department of Nephrology, The First Affiliated Hospital, Zhengzhou University, China.
Biomed Res Int. 2020 Oct 10;2020:7272960. doi: 10.1155/2020/7272960. eCollection 2020.
Bladder cancer (BLCA) is the most common urinary tract tumor and is the 11th most malignant cancer worldwide. With the development of in-depth multisystem sequencing, an increasing number of prognostic molecular markers have been identified. In this study, we focused on the role of protein-coding gene methylation in the prognosis of BLCA. We downloaded BLCA clinical and methylation data from The Cancer Genome Atlas (TCGA) database and used this information to identify differentially methylated genes and construct a survival model using lasso regression. We assessed 365 cases, with complete information regarding survival status, survival time longer than 30 days, age, gender, and tumor characteristics (grade, stage, T, M, N), in our study. We identified 353 differentially methylated genes, including 50 hypomethylated genes and 303 hypermethylated genes. After annotation, a total of 227 genes were differentially expressed. Of these, 165 were protein-coding genes. Three genes (zinc finger protein 382 (), galanin receptor 1 (), and structural maintenance of chromosomes flexible hinge domain containing 1 ()) were selected for the final risk model. Patients with higher-risk scores represent poorer survival than patients with lower-risk scores in the training set (HR = 2.37, 95% CI 1.43-3.94, = 0.001), in the testing group (HR = 1.85, 95% CI 1.16-2.94, = 0.01), and in the total cohort (HR = 2.06, 95% CI 1.46-2.90, < 0.001). Further univariate and multivariate analyses using the Cox regression method were conducted in these three groups, respectively. All the results indicated that risk score was an independent risk factor for BLCA. Our study screened the different methylation protein-coding genes in the BLCA tissues and constructed a robust risk model for predicting the outcome of BLCA patients. Moreover, these three genes may function in the mechanism of development and progression of BLCA, which should be fully clarified in the future.
膀胱癌（BLCA）是最常见的泌尿系统肿瘤，也是全球第 11 大恶性肿瘤。随着深入的多系统测序的发展，越来越多的预后分子标志物被发现。在本研究中，我们专注于蛋白质编码基因甲基化在 BLCA 预后中的作用。我们从癌症基因组图谱（TCGA）数据库下载了 BLCA 的临床和甲基化数据，并使用这些信息来识别差异甲基化基因，并使用lasso 回归构建生存模型。我们评估了 365 例病例，这些病例的生存状态、生存时间超过 30 天、年龄、性别和肿瘤特征（分级、分期、T、M、N）的信息完整。我们鉴定了 353 个差异甲基化基因，包括 50 个低甲基化基因和 303 个高甲基化基因。经过注释，共有 227 个基因表达差异。其中，165 个是蛋白质编码基因。三个基因（锌指蛋白 382（）、甘丙肽受体 1（）和染色体结构维持的柔性铰链域包含 1（））被选入最终的风险模型。在训练集（HR=2.37，95%CI1.43-3.94，=0.001）、测试集（HR=1.85，95%CI1.16-2.94，=0.01）和总队列（HR=2.06，95%CI1.46-2.90，<0.001）中，高风险评分患者的生存情况比低风险评分患者差。进一步在这三组中分别使用 Cox 回归方法进行单变量和多变量分析。所有结果均表明，风险评分是 BLCA 的独立危险因素。我们的研究筛选了 BLCA 组织中的不同甲基化蛋白质编码基因，并构建了一个强大的风险模型，用于预测 BLCA 患者的预后。此外，这三个基因可能在 BLCA 的发展和进展机制中发挥作用，这在未来应该得到充分阐明。
