4.6 Article

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

Journal

AGING-US
Volume 12, Issue 4, Pages 3694-3712

Publisher

IMPACT JOURNALS LLC
DOI: 10.18632/aging.102841

Keywords

clear cell renal cell carcinoma (ccRCC); CIBERSORT; weighted gene co-expression network analysis (WGCNA); CD8(+) T cells; CCL5

Funding

  1. National Natural Science Foundation of China [81672523, 81472404, 81472403, 81272834, 31000572]
  2. 2018 Support Plan for innovative talents in Colleges and Universities of Liaoning Province
  3. Project of Liaoning Province
  4. 2019 Key R & D projects of Shenyang

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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 upregulated 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.

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