Department of Urology, Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University, 758 Hefei Road, Qingdao, Shandong, 266035, China.
Int J Med Sci. 2020 Jun 27;17(11):1610-1624. doi: 10.7150/ijms.46874. eCollection 2020.
Clear cell renal cell carcinoma (ccRCC) is one of the most commonly diagnosed kidney tumors and is often accompanied by immune cell infiltration. In this study, we attempted to identify microenvironment-associated genes and explore the correlation between CXCL13 and tumor-infiltrating immune cells (TIICs). Gene expression profiles and their corresponding clinical information were downloaded from The Cancer Genome Atlas (TCGA) database. The ESTIMATE (Estimation of Stromal and Immune cells in Malignant Tumor tissues using Expression data) algorithm was used to calculate immune cell and stromal cell scores, according to which patients were divided into high- and low-score groups, allowing differentially expressed genes (DEGs) to be identified. Functional enrichment and PPI network analysis were used to identify the functions of the DEGs. CIBERSORT algorithm and TIMER analysis were used to evaluate the immune score. Oncomine and TCGA database were used to explore CXCL13 mRNA expression level in ccRCC. High ESTIMATE score was significantly associated with prognosis. Functional enrichment analysis clarified that DEGs were associated with T cell activation, immune response-regulating cell surface receptor signaling pathway, and positive regulation of cytokine production. PPI network was used to identify CXCL13 as a hub gene. And CIBERSORT algorithm and TIMER analysis showed that strong correlation between CXCL13 expression level and TIICs. Oncomine database was used to validate high CXCL13 expression level in ccRCC tissue, compared to normal tissues. In conclusion, we obtained a list of tumor microenvironment-related genes and identified CXCL13 as an immune response biomarker in patients with ccRCC, GSEA analysis, wound healing and transwell assays showed CXCL13 played a role in tumor migration.
透明细胞肾细胞癌 (ccRCC) 是最常见的诊断为肾肿瘤之一,常伴有免疫细胞浸润。在本研究中,我们试图鉴定与肿瘤微环境相关的基因,并探讨 CXCL13 与肿瘤浸润免疫细胞 (TIICs) 的相关性。从癌症基因组图谱 (TCGA) 数据库下载基因表达谱及其相应的临床信息。根据 ESTIMATE(使用表达数据估计恶性肿瘤组织中的基质和免疫细胞)算法计算免疫细胞和基质细胞评分,根据评分将患者分为高分和低分组,从而确定差异表达基因 (DEGs)。功能富集和 PPI 网络分析用于鉴定 DEGs 的功能。CIBERSORT 算法和 TIMER 分析用于评估免疫评分。Oncomine 和 TCGA 数据库用于探索 ccRCC 中 CXCL13 mRNA 表达水平。高 ESTIMATE 评分与预后显著相关。功能富集分析表明,DEGs 与 T 细胞激活、免疫反应调节细胞表面受体信号通路和细胞因子产生的正调控有关。PPI 网络用于鉴定 CXCL13 作为枢纽基因。CIBERSORT 算法和 TIMER 分析表明,CXCL13 表达水平与 TIICs 之间存在强烈相关性。Oncomine 数据库用于验证 ccRCC 组织中 CXCL13 表达水平高于正常组织。总之,我们获得了一组与肿瘤微环境相关的基因,并鉴定出 CXCL13 是 ccRCC 患者免疫反应的生物标志物,GSEA 分析、划痕愈合和 Transwell 实验表明 CXCL13 在肿瘤迁移中起作用。