LRRK2 is a Candidate Prognostic Biomarker for Clear Cell Renal Cell Carcinoma

Chunxiu Yang,Huan Liu,Jingjing Pang,Huainian Zhang,He Pan,Jian Xu,Shu-Yuan Xiao,Yueying Li

doi:10.2139/ssrn.3802447

Chunxiu Yang, Huan Liu + Show 6 more

Open Access

https://doi.org/10.2139/ssrn.3802447

Copy DOI

Abstract

Background: Clear cell renal cell carcinoma (ccRCC) is the most common malignant tumor of the kidney with high incidence and high morbidity. The study of key genes related to the pathogenesis of ccRCC has become important for gene target therapy. Methods: Bioinformatics analysis of The Cancer Genome Atlas (TCGA) and the NCBI Gene Expression Omnibus (GEO) database were performed to examine the expression pattern and prognostic significance of LRRK2 expression and its relationship to clinical parameters. Immunohistochemistry and Western blot were performed to verify LRRK2 expression. Findings: Bioinformatics analysis showed that LRRK2 expression is up-regulated in ccRCC, which was confirmed in ccRCC tissue immunohistochemically and by protein analysis. The level of expression is 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; protein-protein interaction network analysis showed that LRRK2 interacts with HIF1A and EGFR, suggesting that LRRK2 may also play an important role in the tumorigenesis and progression of ccRCC. Funding Statement: This work was supported by Zhongnan Hospital of Wuhan University Science, Technology and Innovation Seed Fund (znpy2019092).3 Declaration of Interests: The authors have no conflicts of interest to declare. Ethics Approval Statement: This study was reviewed and approved by the Medical Ethical Committee of Zhongnan hospital.

Highlights

Clear cell renal cell carcinoma, derived from renal tubular epithelial cells, is the most common malignant tumor of the kidney
We found that leucine-rich repeat kinase 2 (LRRK2) may play an important role in the tumorigenesis and progression of Clear cell renal cell carcinoma (ccRCC)
Molecular genetic studies have shown that mutations of several genes are associated with the pathogenesis of ccRCC, including von Hippel-Lindau (VHL), set domain-containing 2 (SETD2), BRCA1associated protein-1 (BAP1), polybromo-1 (PBRM1), and lysine-specific histone demethylase 5C (KDM5C) [5,6,7,8], additional genes are being identified to be related to Renal cell carcinoma (RCC) from cancer genomic studies, which may have prognostic, predictive and therapeutic relevance[9]

Summary

Introduction

Clear 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. Renal cell carcinoma (RCC) represents a highly heterogeneous group of tumor, with clear cell renal cell carcinoma (ccRCC) being the most common histologic subtype[1]. Molecular genetic studies have shown that mutations of several genes are associated with the pathogenesis of ccRCC, including von Hippel-Lindau (VHL), set domain-containing 2 (SETD2), BRCA1associated protein-1 (BAP1), polybromo-1 (PBRM1), and lysine-specific histone demethylase 5C (KDM5C) [5,6,7,8], additional genes are being identified to be related to RCC from cancer genomic studies, which may have prognostic, predictive and therapeutic relevance[9]. Myo-inositol monophosphatase 2 (IMPA2) downregulation is correlated with poor prognosis for ccRCC, and miR-25-mediated IMPA2 downregulation may be a potential therapeutic target for preventing the progression and metastatic of ccRCC[11]

Objectives

Methods

Results

Conclusion