Department of Urology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Front Immunol. 2022 Sep 16;13:975057. doi: 10.3389/fimmu.2022.975057. eCollection 2022.
Kidney cancer is one of the most common urological cancers worldwide, and kidney renal clear cell cancer (KIRC) is the major histologic subtype. Our previous study found that von-Hippel Lindau (VHL) gene mutation, the dominant reason for sporadic KIRC and hereditary kidney cancer-VHL syndrome, could affect VHL disease-related cancers development by inducing telomere shortening. However, the prognosis role of telomere-related genes in kidney cancer has not been well discussed. In this study, we obtained the telomere-related genes (TRGs) from TelNet. We obtained the clinical information and TRGs expression status of kidney cancer patients in The Cancer Genome Atlas (TCGA) database, The International Cancer Genome Consortium (ICGC) database, and the Clinical Proteomic Tumor Analysis Consortium (CPTAC) database. Totally 353 TRGs were differential between tumor and normal tissues in the TCGA-KIRC dataset. The total TCGA cohort was divided into discovery and validation TCGA cohorts and then using univariate cox regression, lasso regression, and multivariate cox regression method to conduct data analysis sequentially, ten TRGs (ISG15, RFC2, TRIM15, NEK6, PRKCQ, ATP1A1, ELOVL3, TUBB2B, PLCL1, NR1H3) risk model had been constructed finally. The kidney patients in the high TRGs risk group represented a worse outcome in the discovery TCGA cohort (p<0.001), and the result was validated by these four cohorts (validation TCGA cohort, total TCGA cohort, ICGC cohort, and CPTAC cohort). In addition, the TRGs risk score is an independent risk factor for kidney cancer in all these five cohorts. And the high TRGs risk group correlated with worse immune subtypes and higher tumor mutation burden in cancer tissues. In addition, the high TRGs risk group might benefit from receiving immune checkpoint inhibitors and targeted therapy agents. Moreover, the proteins NEK6, RF2, and ISG15 were upregulated in tumors both at the RNA and protein levels, while PLCL1 and PRKCQ were downregulated. The other five genes may display the contrary expression status at the RNA and protein levels. In conclusion, we have constructed a telomere-related genes risk model for predicting the outcomes of kidney cancer patients, and the model may be helpful in selecting treatment agents for kidney cancer patients.
肾细胞癌是全球最常见的泌尿系统癌症之一，其中肾透明细胞癌（KIRC）是主要的组织学亚型。我们之前的研究发现，von-Hippel Lindau（VHL）基因突变是散发性 KIRC 和遗传性肾癌-VHL 综合征的主要原因，它可以通过诱导端粒缩短来影响 VHL 疾病相关癌症的发展。然而，端粒相关基因在肾癌中的预后作用尚未得到充分讨论。在这项研究中，我们从 TelNet 获得了端粒相关基因（TRGs）。我们从癌症基因组图谱（TCGA）数据库、国际癌症基因组联盟（ICGC）数据库和临床蛋白质组肿瘤分析联盟（CPTAC）数据库中获得了肾癌患者的临床信息和 TRGs 表达状态。在 TCGA-KIRC 数据集的肿瘤组织和正常组织之间有 353 个 TRGs 存在差异。总 TCGA 队列被分为发现和验证 TCGA 队列，然后使用单因素 cox 回归、lasso 回归和多因素 cox 回归方法依次进行数据分析，最终构建了 10 个 TRGs（ISG15、RFC2、TRIM15、NEK6、PRKCQ、ATP1A1、ELOVL3、TUBB2B、PLCL1、NR1H3）风险模型。高 TRGs 风险组的肾癌患者在发现 TCGA 队列中的预后更差（p<0.001），这一结果在四个队列（验证 TCGA 队列、总 TCGA 队列、ICGC 队列和 CPTAC 队列）中得到了验证。此外，在所有五个队列中，TRGs 风险评分都是肾癌的独立危险因素。高 TRGs 风险组与癌症组织中较差的免疫亚型和更高的肿瘤突变负荷相关。此外，高 TRGs 风险组可能受益于接受免疫检查点抑制剂和靶向治疗药物。此外，在 RNA 和蛋白质水平上，肿瘤组织中 NEK6、RF2 和 ISG15 三种蛋白表达上调，PLCL1 和 PRKCQ 表达下调。其他五个基因在 RNA 和蛋白质水平上可能呈现相反的表达状态。总之，我们构建了一个预测肾癌患者预后的端粒相关基因风险模型，该模型可能有助于为肾癌患者选择治疗药物。
Zotero 插件
