Research Paper Volume 12, Issue 4 pp 3694—3712

Identification of biomarkers related to CD8+ T cell infiltration with gene co-expression network in clear cell renal cell carcinoma

Jiaxing Lin 1, *, , Meng Yu 2, *, , Xiao Xu 3, , Yutao Wang 1, , Haotian Xing 1, , Jun An 1, , Jieping Yang 1, , Chaozhi Tang 1, , Dan Sun 1, , Yuyan Zhu 1, ,

  • 1 Department of Urology, The First Hospital of China Medical University, Shenyang 110001, Liaoning, China
  • 2 Department of Reproductive Biology and Transgenic Animal, China Medical University, Shenyang 110001, Liaoning, China
  • 3 Department of Pediatric Intensive Care Unit, The Shengjing Hospital of China Medical University, Shenyang 110001, Liaoning, China
* Equal contribution

received: October 1, 2019 ; accepted: February 4, 2020 ; published: February 20, 2020 ;

https://doi.org/10.18632/aging.102841
How to Cite

Copyright © 2020 Lin et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Clear cell renal cell carcinoma (ccRCC) is an extremely common kind of kidney cancer in adults. Immunotherapy and targeted therapy are particularly effective at treating ccRCC. In this study, weighted gene co-expression network analysis and a deconvolution algorithm that quantifies the cellular composition of immune cells were used to analyze ccRCC expression data from the Gene Expression Omnibus database, and identify modules related to CD8+ T cells. Ten hub genes (LCK, CD2, CD3D, CD3G, IRF1, IFNG, CCR5, CD8A, CCL5, and CXCL9) were identified by co-expression network and protein-protein interactions network analysis. Datasets obtained from The Cancer Genome Atlas were analyzed and the data revealed that the hub genes were meaningfully up-regulated in tumor tissues and correlated with promotion of tumor progression. After Kaplan-Meier analysis and Oncomine meta-analysis, CCL5 was selected as a prognostic biomarker. Finally, the experimental results show that reduced expression of CCL5 decreased cell proliferation and invasion in the ccRCC cell line. Various analyses were performed and verified, CCL5 is a potential biomarker and therapeutic target which related to CD8+ T cell infiltration in ccRCC.

Abbreviations

ccRCC: Clear cell renal cell carcinoma; WGCNA: Weighted gene co-expression network analysis; CIBERSORT: Cell-type identification by estimating relative subsets of RNA transcripts; TIICs: Tumor-infiltrating immune cells; PPI: Protein-protein interactions. GEO: Gene Expression Omnibus; TCGA: The Cancer Genome Atlas; GSEA: Gene set enrichment analysis.