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Int J Biol Sci 2018; 14(3):266-279. doi:10.7150/ijbs.23574

Research Paper

Identification of key genes and pathways in human clear cell renal cell carcinoma (ccRCC) by co-expression analysis

Lushun Yuan1,2,#, Guang Zeng1,#, Liang Chen1, Gang Wang1,2,3, Xiaolong Wang4, Xinyue Cao3, Mengxin Lu1, Xuefeng Liu5, Guofeng Qian6, Yu Xiao1,3,7✉, Xinghuan Wang1,2✉

1. Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, China
2. Medical Research Institute, School of Medicine, Wuhan University, Wuhan, China.
3. Department of Biological Repositories, Zhongnan Hospital of Wuhan University, Wuhan, China
4. Department of Urology, Ludwig-Maximilians-University Munich, Munich, Germany
5. Department of Pathology, Lombardi Comprehensive Cancer Center, Georgetown University Medical School, Washington DC, USA
6. Department of Endocrinology, The First Affiliated Hospital of Zhejiang University, Hangzhou, China
7. Laboratory of Precision Medicine, Zhongnan Hospital of Wuhan University, Wuhan, China
#These authors contributed equally to this work.


Human clear cell renal cell carcinoma (ccRCC) is the most common solid lesion within kidney, and its prognostic is influenced by the progression covering a complex network of gene interactions. In our study, we screened differential expressed genes, and constructed protein-protein interaction (PPI) network and a weighted gene co-expression network to identify key genes and pathways associated with the progression of ccRCC (n = 56). Functional and pathway enrichment analysis demonstrated that upregulated differentially expressed genes (DEGs) were significantly enriched in response to wounding, positive regulation of immune system process, leukocyte activation, immune response and cell activation. Downregulated DEGs were significantly enriched in oxidation reduction, monovalent inorganic cation transport, ion transport, excretion and anion transport. In the PPI network, top 10 hub genes were identified (TOP2A, MYC, ALB, CDK1, VEGFA, MMP9, PTPRC, CASR, EGFR and PTGS2). In co-expression network, 6 ccRCC-related modules were identified. They were associated with immune response, metabolic process, cell cycle regulation, angiogenesis and ion transport. In conclusion, our study illustrated the hub genes and pathways involved in the progress of ccRCC, and further molecular biological experiments are needed to confirm the function of the candidate biomarkers in human ccRCC.

Keywords: clear cell renal cell carcinoma (ccRCC), differentially expressed genes (DEGs), biomarker, weighted gene co-expression network analysis (WGCNA), protein-protein interaction (PPI)

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license ( See for full terms and conditions.
How to cite this article:
Yuan L, Zeng G, Chen L, Wang G, Wang X, Cao X, Lu M, Liu X, Qian G, Xiao Y, Wang X. Identification of key genes and pathways in human clear cell renal cell carcinoma (ccRCC) by co-expression analysis. Int J Biol Sci 2018; 14(3):266-279. doi:10.7150/ijbs.23574. Available from