Int J Med Sci 2020; 17(11):1610-1624. doi:10.7150/ijms.46874

Research Paper

Association of CXCL13 and Immune Cell Infiltration Signature in Clear Cell Renal Cell Carcinoma

Fangdong Jiao, Hao Sun, Qingya Yang, Hui Sun, Zehua Wang, Ming Liu, Jun Chen

Department of Urology, Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University, 758 Hefei Road, Qingdao, Shandong, 266035, China.

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Citation:
Jiao F, Sun H, Yang Q, Sun H, Wang Z, Liu M, Chen J. Association of CXCL13 and Immune Cell Infiltration Signature in Clear Cell Renal Cell Carcinoma. Int J Med Sci 2020; 17(11):1610-1624. doi:10.7150/ijms.46874. Available from http://www.medsci.org/v17p1610.htm

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Abstract

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.

Keywords: Clear cell renal cell carcinoma, immune cell infiltration signature, CXCL13, TCGA