LRRK2 is a candidate prognostic biomarker for clear cell renal cell carcinoma

Cancer Cell International

Chunxiu Yang¹  Jingjing Pang¹  Jian Xu¹  He Pan¹  Huan Liu¹  Huainian Zhang¹  Yueying Li¹  Shu-Yuan Xiao² 

[1] Department of Pathology, Zhongnan Hospital of Wuhan University, Wuhan, China;Wuhan University Center for Pathology and Molecular Diagnostics, Wuhan, China;Department of Pathology, Zhongnan Hospital of Wuhan University, Wuhan, China;Wuhan University Center for Pathology and Molecular Diagnostics, Wuhan, China;Department of Pathology, University of Chicago Medicine, Chicago, IL, USA;

关键词: LRRK2;    Clear cell renal cell carcinoma;    Bioinformatic analysis;    Prognosis biomarker;    HIF1A;    EGFR;    Tumorigenesis;    Pathology;   

DOI  :  10.1186/s12935-021-02047-y

来源: Springer

【 摘 要 】

BackgroundClear cell renal cell carcinoma (ccRCC), derived from renal tubular epithelial cells, is the most common malignant tumor of the kidney. The study of key genes related to the pathogenesis of ccRCC has become important for gene target therapy.MethodsBioinformatics analysis of The Cancer Genome Atlas (TCGA), the NCBI Gene Expression Omnibus (GEO) database, USUC Xena database, cBioPortal for Cancer Genomics, and MethSurv were performed to examine the aberrant genetic pattern and prognostic significance of leucine-rich repeat kinase 2 (LRRK2) expression and its relationship to clinical parameters. Immunohistochemistry and Western blot were performed to verify LRRK2 expression. The regulation of ccRCC tumor cell lines proliferation by LRRK2 was examined by CCK8 assay.ResultsBioinformatics analysis showed that LRRK2 expression was up-regulated and largely correlated with DNA methylation in ccRCC. The up-regulation of LRRK2 was confirmed in ccRCC tissue immunohistochemically and by protein analysis. The level of expression was related to gender, pathological grade, stage, and metastatic status of ccRCC patients. Meanwhile, Kaplan–Meier analysis showed that high expression of LRRK2 correlates to a better prognosis; knockdown of LRRK2 expression attenuated the proliferation ability of ccRCC tumor cell lines; protein–protein interaction network analysis showed that LRRK2 interacts with HIF1A and EGFR.ConclusionWe found that LRRK2 may play an important role in the tumorigenesis and progression of ccRCC. Our findings provided a potential predictor and therapeutic target in ccRCC.

【 授权许可】

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