Department of Nephrology, The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou 510632, China.
Department of Nephrology, The Second People's Hospital of Lianping County, Heyuan, China.
Biomed Res Int. 2020 Jan 11;2020:4030915. doi: 10.1155/2020/4030915. eCollection 2020.
The present techniques of clinical and histopathological diagnosis hardly distinguish chromophobe renal cell carcinoma (ChRCC) from renal oncocytoma (RO). To identify differentially expressed genes (DEGs) as effective biomarkers for diagnosis and prognosis of ChRCC and RO, three mRNA microarray datasets (GSE12090, GSE19982, and GSE8271) were downloaded from the GEO database. Functional enrichment analysis of DEGs was performed by DAVID. STRING and Cytoscape were applied to construct the protein-protein interaction (PPI) network and key modules of DEGs. Visualized plots were conducted by the R language. We downloaded clinical data from the TCGA database and the influence of key genes on the overall survival of ChRCC was performed by Kaplan-Meier and Cox analyses. Gene set enrichment analysis (GSEA) was utilized in exploring the function of key genes. A total of 79 DEGs were identified. Enrichment analyses revealed that the DEGs are closely related to tissue invasion and metastasis of cancer. Subsequently, 14 hub genes including ESRP1, AP1M2, CLDN4, and CLDN7 were detected. Kaplan-Meier analysis indicated that the low expression of CLDN7 and GNAS was related to the worse overall survival in patients with ChRCC. Univariate Cox analysis showed that CLDN7 might be a helpful biomarker for ChRCC prognosis. Subgroup analysis revealed that the expression of CLDN7 showed a downtrend with the development of the clinical stage, topography, and distant metastasis of ChRCC. GSEA analysis identified that cell adhesion molecules cams, B cell receptor signaling pathway, T cell receptor signaling pathway, RIG-I like receptor signaling pathway, Toll-like receptor signaling pathway, and apoptosis pathway were associated with the expression of CLDN7. In conclusion, ESRP1, AP1M2, CLDN4, PRSS8, and CLDN7 were found to distinguish ChRCC from RO. Besides, the low expression of CLDN7 was closely related to ChRCC progression and could serve as an independent risk factor for the overall survival in patients with ChRCC.
目前的临床和组织病理学诊断技术几乎无法区分嫌色细胞肾细胞癌 (ChRCC) 和肾嗜酸细胞瘤 (RO)。为了鉴定差异表达基因 (DEGs) 作为 ChRCC 和 RO 诊断和预后的有效生物标志物,从 GEO 数据库中下载了三个 mRNA 微阵列数据集 (GSE12090、GSE19982 和 GSE8271)。通过 DAVID 进行 DEGs 的功能富集分析。应用 STRING 和 Cytoscape 构建蛋白质-蛋白质相互作用 (PPI) 网络和 DEGs 的关键模块。通过 R 语言进行可视化绘图。从 TCGA 数据库中下载临床数据,并通过 Kaplan-Meier 和 Cox 分析研究关键基因对 ChRCC 总生存率的影响。基因集富集分析 (GSEA) 用于探索关键基因的功能。共鉴定出 79 个 DEGs。富集分析表明,DEGs 与癌症的组织侵袭和转移密切相关。随后,检测到包括 ESRP1、AP1M2、CLDN4 和 CLDN7 在内的 14 个关键基因。Kaplan-Meier 分析表明,CLDN7 的低表达与 ChRCC 患者总体生存率较差有关。单因素 Cox 分析表明,CLDN7 可能是 ChRCC 预后的有用生物标志物。亚组分析表明,CLDN7 的表达随着 ChRCC 临床分期、肿瘤部位和远处转移的发展呈下降趋势。GSEA 分析表明,细胞黏附分子 cams、B 细胞受体信号通路、T 细胞受体信号通路、RIG-I 样受体信号通路、Toll 样受体信号通路和细胞凋亡通路与 CLDN7 的表达相关。总之,ESRP1、AP1M2、CLDN4、PRSS8 和 CLDN7 被发现可区分 ChRCC 和 RO。此外,CLDN7 的低表达与 ChRCC 的进展密切相关,可作为 ChRCC 患者总生存率的独立危险因素。