Investig Clin Urol.  2022 Jan;63(1):107-117. 10.4111/icu.20210273.

Identification of adhesion-associated extracellular matrix component thrombospondin 3 as a prognostic signature for clear cell renal cell carcinoma

Affiliations
  • 1Guangdong Provincial Key Laboratory of Systems Biology and Synthetic Biology for Urogenital Tumors, Department of Urology, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People’s Hospital, Shenzhen Institute of Translational Medicine, Shenzhen, China
  • 2henzhen Key Laboratory of Genitourinary Tumor, Department of Urology, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People’s Hospital, Shenzhen Institute of Translational Medicine, Shenzhen, China
  • 3Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China
  • 4Department of Minimally Invasive Intervention, Peking University Shenzhen Hospital, Shenzhen, China
  • 5State Key Laboratory of Cell Biology, CAS Key Laboratory of Systems Biology, CAS Center for Excellence in Molecular Cell Science, Innovation Center for Cell Signaling Network, Shanghai Institute of Biochemistry and Cell Biology, University of Chinese Academy of Sciences, Shanghai, China
  • 6Department of Biology, NO.6 Middle School of Changsha, Changsha, China

Abstract

Purpose
Clear cell renal cell carcinoma (ccRCC) is a highly aggressive disease, and approximately 30% of patients are diagnosed at the metastatic stage. Even with targeted therapies, the prognosis of advanced ccRCC is poor. The aim of this study was to investigate clinical prognosis signatures by analyzing the ccRCC datasets in The Cancer Genome Atlas (TCGA) and the Clinical Proteomic Tumor Analysis Consortium (CPTAC) and the function of thrombospondin 3 (THBS3 ) in ccRCC.
Materials and Methods
We analyzed the ccRCC datasets in TCGA and CPTAC to search for extracellular matrix (ECM)-related and adhesion-associated genes, and conducted overall survival, Cox, and receiver operating characteristic analyses. We also performed CCK8, colony formation, and transwell assays to compared the proliferation and migration ability of THBS3 knockout cells with those of cells without THBS3 knockout.
Results
Comprehensive bioinformatics analysis revealed that THBS3 is a novel candidate oncogene that is overexpressed in ccRCC tumor tissue and that its elevated expression indicates poor prognosis. Our study also showed that knockdown of THBS3 inhibits proliferation, colony formation, and migration of ccRCC cells.
Conclusions
In summary, our data have revealed that THBS3 is upregulated in cancer tissues and could be used as a novel prognostic marker for ccRCC. Our findings thus offer theoretical support with bioinformatics analyses to the study of ECM and adhesion proteins in ccRCC, which may provide a new perspective for the clinical management of ccRCC.

Keyword

Clear cell renal cell carcinoma; Human; Metastasis; Thrombospondin 3 protein
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