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Identification of gene markers associated with metastasis in clear cell renal cell carcinoma.

ABSTRACT: The present study aimed to screen potential target genes for the early diagnosis and treatment of early metastatic clear cell renal cell carcinoma (ccRCC) using the microarray data of early metastatic and non-metastatic ccRCC samples. The DNA microarray dataset GSE47352 was downloaded from Gene Expression Omnibus and included 4 early metastatic and 5 non-metastatic ccRCC samples. Differentially expressed genes (DEGs) were screened using the limma package. Then, pheatmap package was used to conduct two-way clustering for the DEGs. Subsequently, MAPPFinder and GenMAPP were employed separately to perform functional and pathway enrichment analysis for the DEGs. Additionally, a protein-protein interaction (PPI) network was constructed using Cytoscape, and small drug molecules were searched using Connectivity map (cmap). In total, 196 upregulated and 163 downregulated genes were identified. DEGs, including JUN, tumor necrosis factor (TNF), Ras homolog family member B (RHOB) and transforming growth factor ?2 (TGF?2) were significantly enriched in the signaling pathway of renal cell carcinoma. Furthermore, nuclear receptor subfamily 4 group A member 1 (NR4A1) was significantly enriched in the mitogen-activated protein kinase signaling pathway; in addition, laminin subunit ? (LAMA) 1, LAMA2 and LAMA4 were significantly enriched in extracellular matrix-receptor interaction. JUN (degree=6) had the highest degree in the PPI network. Thapsigargin (score=-0.913) possessed the highest performance in terms of the treatment of early metastatic ccRCC. In the present study, it was discovered that certain DEGs, including JUN, TNF, RHOB, NR4A1, TGF?2, LAMA1, LAMA2 and LAMA4 were potential target genes associated with early metastatic ccRCC. In addition, thapsigargin could be used as an efficient small drug molecule for the treatment of early metastatic ccRCC.

SUBMITTER: Yang H

PROVIDER: S-EPMC5453167 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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Identification of gene markers associated with metastasis in clear cell renal cell carcinoma.

Yang Hailing H Huo Pengfei P Hu Guozhang G Wei Bo B Kong Dalian D Li Hongjun H

Oncology letters 20170424 6

The present study aimed to screen potential target genes for the early diagnosis and treatment of early metastatic clear cell renal cell carcinoma (ccRCC) using the microarray data of early metastatic and non-metastatic ccRCC samples. The DNA microarray dataset GSE47352 was downloaded from Gene Expression Omnibus and included 4 early metastatic and 5 non-metastatic ccRCC samples. Differentially expressed genes (DEGs) were screened using the limma package. Then, pheatmap package was used to condu ...[more]

PMID: 28599476

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Project description:BackgroundClear cell renal cell carcinoma (ccRCC) is a tumor that frequently shows the hematogenous pathway and tends to be resistant to radiotherapy and chemotherapy. However, the exact mechanism of ccRCC metastasis remains unknown.MethodsDifferentially expressed genes (DEGs) of three gene expression profiles (GSE85258, GSE105288 and GSE22541) downloaded from the Gene Expression Omnibus (GEO) database were analyzed by GEO2R analysis, and co-expressed DEGs among the datasets were identified using a Venn drawing tool. The co-expressed DEGs were investigated using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis, and hub genes were determined based on the protein-protein interaction network established by STRING. After survival analysis performed on UALCAN website, possible key genes were selected and verified in ccRCC cell lines and ccRCC tissues (n = 44). Statistical analysis was conducted using GraphPad Prism (Version 8.1.1).ResultsA total of 104 co-expressed DEGs were identified in the three datasets. Pathway analysis revealed that these genes were enriched in the extracellular matrix (ECM)-receptor interaction, protein digestion and absorption and focal adhesion. Survival analysis on 17 hub genes revealed that four key genes with a significant impact on survival: procollagen C-endopeptidase enhancer (PCOLCE), prolyl 4-hydroxylase subunit beta (P4HB), collagen type VI alpha 2 (COL6A2) and collagen type VI alpha 3 (COL6A3). Patients with higher expression of these key genes had worse survival than those with lower expression. In vitro experiments revealed that the mRNA expression levels of PCOLCE, P4HB and COL6A2 were three times higher and that of COL6A3 mRNA was 16 times higher in the metastatic ccRCC cell line Caki-1 than the corresponding primary cell line Caki-2. Immunohistochemistry revealed higher expression of the proteins encoded by these four genes in metastatic ccRCC compared with tumors from the corresponding primary sites, with statistical significance.ConclusionPCOLCE, P4HB, COL6A2 and COL6A3 are upregulated in metastatic ccRCC and might be related to poor prognosis and distant metastases.

Dataset Information

Identification of gene markers associated with metastasis in clear cell renal cell carcinoma.

Publications

Identification of gene markers associated with metastasis in clear cell renal cell carcinoma.

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