Association of CXCL13 and Immune Cell Infiltration Signature in Clear Cell Renal Cell Carcinoma
Association of CXCL13 and Immune Cell Infiltration Signature in Clear Cell Renal Cell Carcinoma
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DOI：
10.7150/ijms.46874
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发表时间：
2020-01-01
影响因子：
3.6
通讯作者：
Chen, Jun
中科院分区：
文献类型：
--
作者：
Jiao, Fangdong;Sun, Hao;Chen, Jun
透明细胞肾细胞癌（ccRCC）是最常诊断的肾脏肿瘤之一，通常伴有免疫细胞浸润。在这项研究中，我们试图识别微环境相关基因，并探讨CXCL13与肿瘤浸润免疫细胞（TIICs）之间的相关性。基因表达谱及其相应的临床信息从癌症基因组图谱（TCGA）数据库下载。使用ESTIMATE（使用表达数据估计恶性肿瘤组织中的基质细胞和免疫细胞）算法计算免疫细胞和基质细胞评分，根据该评分将患者分为高分组和低分组，以识别差异表达基因（DEG）。功能富集和PPI网络分析用于确定DEG的功能。免疫评分采用CIBERSORT算法和TIMER分析。采用Oncomine和TCGA数据库检测ccRCC中CXCL13 mRNA的表达水平。高ESTIMATE评分与预后显著相关。功能富集分析阐明DEG与T细胞活化、免疫应答调节细胞表面受体信号通路以及细胞因子产生的正调节相关。PPI网络用于将CXCL13鉴定为枢纽基因。CIBERSORT算法和TIMER分析显示，CXCL13表达水平与TIICs之间存在较强的相关性。Oncomine数据库用于验证与正常组织相比，ccRCC组织中的高CXCL13表达水平。总之，我们获得了一系列肿瘤微环境相关基因，并将CXCL13鉴定为ccRCC患者的免疫应答生物标志物，GSEA分析、伤口愈合和transwell测定显示CXCL13在肿瘤迁移中发挥作用。
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.