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

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Chunxiu Yang ◽  
Jingjing Pang ◽  
Jian Xu ◽  
He Pan ◽  
Yueying Li ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Tumor Cell ◽  
Cell Carcinoma ◽  
Cell Lines ◽  
Renal Cell ◽  
Bioinformatics Analysis ◽  
Clear Cell ◽  
Tumor Cell Lines ◽  
Cell Renal Cell Carcinoma ◽  
Gene Target

Abstract Background 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. Methods Bioinformatics 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. Results Bioinformatics 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. Conclusion We 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.

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

2021 ◽  
Author(s):  
Chunxiu Yang ◽  
Jingjing Pang ◽  
Jian Xu ◽  
He Pan ◽  
Yueying Li ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Bioinformatics Analysis ◽  
Clear Cell ◽  
Target Therapy ◽  
Prognostic Significance ◽  
The Cancer Genome Atlas ◽  
Cell Renal Cell Carcinoma ◽  
Gene Target

Abstract Background: 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. 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 leucine-rich repeat kinase 2 (LRRK2) expression and its relationship to clinical parameters. Immunohistochemistry and Western blot were performed to verify LRRK2 expression.Results: Bioinformatics analysis showed that LRRK2 expression was up-regulated in ccRCC, which 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; protein-protein interaction network analysis showed that LRRK2 interacts with HIF1A and EGFR.Conclusion: We 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.

scholarly journals IgG is involved in the migration and invasion of clear cell renal cell carcinoma

2015 ◽  
Vol 69 (6) ◽  
pp. 497-504 ◽  
Author(s):  
Zhengzuo Sheng ◽  
Yang Liu ◽  
Caipeng Qin ◽  
Zhenhua Liu ◽  
Yeqing Yuan ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Western Blot ◽  
Cell Carcinoma ◽  
Cell Lines ◽  
Renal Cell ◽  
Clear Cell ◽  
Migration And Invasion ◽  
Cancer Therapies ◽  
Normal Kidney ◽  
Cell Renal Cell Carcinoma

OBJECTIVE:To investigate if IgG can be expressed in clear cell renal cell carcinoma (cRCC) , and the expression of IgG is involved in the cancer progression. If IgG expression can serve as a potential target in cancer therapies and be used for judging the prognosis.MATERIALS AND METHODS:By immunohistochemistry, we detected IgG in cRCC tissues(75 cRCC tissues and75 adjacent normal kidney tissues). Immunofluorescence and Western blot was used to detect the IgG in cRCC cell lines (786-0, ACHN and CAKI-I). By RT-PCR, the functional transcript of IgG heavy chain was detected. Knockdown of IgG was to analyze the proliferation, migration and invasion ability by CCK8, Transwell and Matrigel and apoptosis in cRCC cell lines.RESULTS:By immunohistochemistry, we found strong staining of IgG in 66 cases of 75 cRCC tissues and 63 cases of 75 adjacent normal kidney tissues. Immunofluorescence and Western blot was found IgG in cRCC cell lines. Knock-down IgG in cRCC cell lines resulted in significant inhibition of cell proliferation, migration and invasion, and the induction of apoptosis of the 786-0 cells. The immunohistochemistry analysis showed that high IgG expression significantly correlated with the poor differentiation and advanced stage of cRCC.CONCLUSION:IgG was over expressed in cRCC and was involved in the proliferation, migration and invasion of cancer cells. IgG expression may serve as a potential target in cancer therapies and could be used for judging the prognosis.

Identification of potential key genes and key pathways related to clear cell renal cell carcinoma through bioinformatics analysis

2020 ◽  
Vol 52 (8) ◽  
pp. 853-863
Author(s):  
Wenxin Zhai ◽  
Haijiao Lu ◽  
Shenghua Dong ◽  
Jing Fang ◽  
Zhuang Yu
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Phosphoenolpyruvate Carboxykinase ◽  
Bioinformatics Analysis ◽  
Clear Cell ◽  
Interaction Network ◽  
Polymerase Chain Reaction Analysis ◽  
Cell Renal Cell Carcinoma ◽  
Key Genes

Abstract Clear cell renal cell carcinoma (ccRCC) is a common malignancy of the genitourinary system and is associated with high mortality rates. However, the molecular mechanism of ccRCC pathogenesis is still unclear, which translates to few effective diagnostic and prognostic biomarkers. In this study, we conducted a bioinformatics analysis on three Gene Expression Omnibus datasets and identified 437 differentially expressed genes (DEGs) related to ccRCC development and prognosis, of which 311 and 126 genes are respectively down-regulated and up-regulated. The protein–protein interaction network of these DEGs consists of 395 nodes and 1872 interactions and 2 prominent modules. The Staphylococcus aureus infection and complement and coagulation cascades are significantly enriched in module 1 and are likely involved in ccRCC progression. Forty-two hub genes were screened, of which von Willebrand factor, TIMP metallopeptidase inhibitor 1, plasminogen, formimidoyltransferase cyclodeaminase, solute carrier family 34 member 1, hydroxyacid oxidase 2, alanine-glyoxylate aminotransferase 2, phosphoenolpyruvate carboxykinase 1, and 3-hydroxy-3-methylglutaryl-CoA synthase 2 are possibly related to the prognosis of ccRCC. The differential expression of all nine genes was confirmed by quantitative real-time polymerase chain reaction analysis of the ccRCC and normal renal tissues. These key genes are potential biomarkers for the diagnosis and prognosis of ccRCC and warrant further investigation.

scholarly journals PPARα gene is a diagnostic and prognostic biomarker in clear cell renal cell carcinoma by integrated bioinformatics analysis

2019 ◽  
Vol 10 (10) ◽  
pp. 2319-2331
Author(s):  
Yongwen Luo ◽  
Liang Chen ◽  
Gang Wang ◽  
Guofeng Qian ◽  
Xuefeng Liu ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Bioinformatics Analysis ◽  
Clear Cell ◽  
Prognostic Biomarker ◽  
Cell Renal Cell Carcinoma

scholarly journals Various forms of HIF ‐1α protein characterize the clear cell renal cell carcinoma cell lines

IUBMB Life ◽  
2020 ◽  
Vol 72 (6) ◽  
pp. 1220-1232
Author(s):  
Monika Swiatek ◽  
Iga Jancewicz ◽  
Jakkapong Kluebsoongnoen ◽  
Renata Zub ◽  
Anna Maassen ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Cell Lines ◽  
Renal Cell ◽  
Clear Cell ◽  
Carcinoma Cell ◽  
Cell Renal Cell Carcinoma ◽  
Renal Cell Carcinoma Cell ◽  
Carcinoma Cell Lines

scholarly journals Tumor Cell and Tumor Vasculature Expression of B7-H3 Predict Survival in Clear Cell Renal Cell Carcinoma

2008 ◽  
Vol 14 (16) ◽  
pp. 5150-5157 ◽  
Author(s):  
Paul L. Crispen ◽  
Yuri Sheinin ◽  
Timothy J. Roth ◽  
Christine M. Lohse ◽  
Susan M. Kuntz ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Tumor Cell ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Tumor Vasculature ◽  
Cell Renal Cell Carcinoma

scholarly journals Acyl-CoA Thioesterase 8 and 11 as Novel Biomarkers for Clear Cell Renal Cell Carcinoma

2020 ◽  
Vol 11 ◽  
Author(s):  
Chao-Liang Xu ◽  
Lei Chen ◽  
Deng Li ◽  
Fei-Teng Chen ◽  
Ming-Lei Sha ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Correlation Analysis ◽  
Cell Carcinoma ◽  
Cell Lines ◽  
Renal Cell ◽  
Clear Cell ◽  
Functional Enrichment ◽  
Clinical Samples ◽  
Cell Renal Cell Carcinoma ◽  
Ccrcc Cell

BackgroundClear cell renal cell carcinoma (ccRCC) is essentially a metabolic disorder characterized by reprogramming of several metabolic pathways. Acyl-coenzyme A thioesterases (ACOTs) are critical enzymes involved in fatty acid metabolism; however, the roles of ACOTs in ccRCC remain unclear. This study explored ACOTs expressions and their diagnostic and prognostic values in ccRCC.MethodsThree online ccRCC datasets from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) were utilized to measure the expressions of ACOTs in paired normal and tumor tissues. Receiver operating characteristic (ROC) curves were depicted to assess the diagnostic values of ACOTs in ccRCC. Quantitative real-time PCR and immunohistochemical analysis were performed to validate the ACOT11 expression in ccRCC cell lines and clinical samples. Survival curves and Cox regression analysis were used to evaluate the predictive values of ACOTs in clinical outcome of ccRCC patients. Functional enrichment analyses and correlation analysis were carried out to predict the potential roles of ACOT8 in tumorigenesis and progression of ccRCC.ResultsACOT1/2/8/11/13 were found to be significantly downregulated in ccRCC samples. In particular, ACOT11 was decreased in almost every matched normal-tumor pair, and had extremely high diagnostic value as shown by ROC curve analysis (AUC = 0.964). The expression of ACOT11 was further verified in ccRCC cell lines and clinical samples at mRNA and protein levels. Furthermore, clinical correlation analysis and survival analysis indicated that ACOT8 was correlated with disease progression and was an independent predictor of unfavorable outcome in ccRCC. Moreover, functional analyses suggested potential roles of ACOT8 in the regulation of oxidative phosphorylation (OXPHOS), and correlation analysis revealed an association between ACOT8 and ferroptosis-related genes in ccRCC.ConclusionOur study revealed that ACOT11 and ACOT8 are promising biomarkers for diagnosis and prognosis of ccRCC, respectively, and ACOT8 may affect ccRCC development and progression through the regulation of OXPHOS and ferroptosis. These findings may provide new strategies for precise diagnosis and personalized therapy of ccRCC.

scholarly journals Identification of Four Pathological Stage-Relevant Genes in Association with Progression and Prognosis in Clear Cell Renal Cell Carcinoma by Integrated Bioinformatics Analysis

2020 ◽  
Vol 2020 ◽  
pp. 1-16
Author(s):  
Dengyong Xu ◽  
Yuzi Xu ◽  
Yiming Lv ◽  
Fei Wu ◽  
Yunlong Liu ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Early Diagnosis ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Molecular Mechanisms ◽  
Bioinformatics Analysis ◽  
Clear Cell ◽  
Clinical Stage ◽  
Hub Genes ◽  
Cell Renal Cell Carcinoma

Clear cell renal cell carcinoma (ccRCC) is a major histological subtype of renal cell carcinoma and can be clinically divided into four stages according to the TNM criteria. Identifying clinical stage-related genes is beneficial for improving the early diagnosis and prognosis of ccRCC. By using bioinformatics analysis, we aim to identify clinical stage-relevant genes that are significantly associated with the development of ccRCC. First, we analyzed the gene expression microarray data sets: GSE53757 and GSE73731. We divided these data into five groups by staging information—normal tissue and ccRCC stages I, II, III, and IV—and eventually identified 500 differentially expressed genes (DEGs). To obtain precise stage-relevant genes, we subsequently applied weighted gene coexpression network analysis (WGCNA) to the GSE73731 dataset and KIRC data from The Cancer Genome Atlas (TCGA). Two modules from each dataset were identified to be related to the tumor TNM stage. Several genes with high inner connection inside the modules were considered hub genes. The intersection results between hub genes of key modules and 500 DEGs revealed UBE2C, BUB1B, RRM2, and TPX2 as highly associated with the stage of ccRCC. In addition, the candidate genes were validated at both the RNA expression level and the protein level. Survival analysis also showed that 4 genes were significantly correlated with overall survival. In conclusion, our study affords a deeper understanding of the molecular mechanisms associated with the development of ccRCC and provides potential biomarkers for early diagnosis and individualized treatment for patients at different stages of ccRCC.

scholarly journals Identification of significant genes with prognostic influence in clear cell renal cell carcinoma via bioinformatics analysis

2020 ◽  
Vol 9 (2) ◽  
pp. 452-461
Author(s):  
Fangyuan Zhang ◽  
Pengjie Wu ◽  
Yalong Wang ◽  
Mengxian Zhang ◽  
Xiaodan Wang ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Bioinformatics Analysis ◽  
Clear Cell ◽  
Cell Renal Cell Carcinoma

scholarly journals CircUBAP2 Inhibits Proliferation and Metastasis of Clear Cell Renal Cell Carcinoma via Targeting miR-148a-3p/FOXK2 Pathway

2020 ◽  
Vol 29 ◽  
pp. 096368972092575
Author(s):  
Jiping Sun ◽  
Aiping Yin ◽  
Wenjing Zhang ◽  
Jia Lv ◽  
Yu Liang ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Cell Lines ◽  
Renal Cell ◽  
Clear Cell ◽  
Underlying Mechanism ◽  
Migration And Invasion ◽  
Inhibitory Effects ◽  
Cell Renal Cell Carcinoma ◽  
Ribonucleic Acids

Clear cell renal cell carcinoma (ccRCC) is the prominent histological subtype of renal cell carcinoma (RCC) with high incidence of local recurrence and distant metastasis. It has been documented that circular ribonucleic acids (circRNAs) play crucial roles in the development of cancers; however, study on exploring the role of circRNAs in ccRCC still remains limited. In the present study, we aimed to evaluate the biological function of a novel circRNA UBAP2 (circUBAP2) in ccRCC and the underlying mechanism. Our results showed that circUBAP2 expression was significantly down-regulated in ccRCC tissues and cell lines. Overexpression of circUBAP2 significantly inhibited the proliferation, migration, and invasion of ccRCC cells. MiR-148a-3p was a target miRNA of circUBAP2 in ccRCC cells, and its expression levels in ccRCC tissues and cell lines were negatively correlated with circUBAP2 levels. Moreover, miR-148a-3p reversed the inhibitory effects of circUBAP2 on cell proliferation, migration, and invasion in ccRCC cells. Additionally, forkhead box K2 (FOXK2) was found to be a target gene of miR-148a-3p and regulated by miR-148a-3p in ccRCC cells. Furthermore, knockdown of FOXK2 reversed the inhibitory effects of miR-148a-3p inhibitor on ccRCC cells. In conclusion, these findings indicated that circUBAP2 functioned as a novel tumor suppressor in ccRCC through regulating the miR-148a-3p/FOXK2 axis. Therefore, circUBAP2 might serve as a potential therapeutic target for the treatment of ccRCC.

Sign in / Sign up

Export Citation Format

Share Document