Bioinformatic identification of key genes and analysis of prognostic values in clear cell renal cell carcinoma.

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Three expression profiles (GSE36895, GSE46699 and GSE71963) were collected from Gene Expression Omnibus. GEO2R was used to identify differentially expressed genes (DEGs) in ccRCC tissues and normal samples. The Database for Annotation, Visualization and Integrated Discovery was utilized for functional and pathway enrichment analysis. STRING v10.5 and Molecular Complex Detection were used for protein-protein interaction (PPI) network construction and module analysis, respectively. Regulation network analyses were performed with the WebGestal tool. UALCAN web-portal was used for expression validation and survival analysis of hub genes in ccRCC patients from The Cancer Genome Atlas (TCGA). A total of 65 up- and 164 downregulated genes were identified as DEGs. DEGs were enriched with functional terms and pathways compactly related to ccRCC pathogenesis. Seventeen hub genes and one significant module were filtered out and selected from the PPI network. The differential expression of hub genes was verified in TCGA patients. Kaplan-Meier plot showed that high mRNA expression of enolase 2 (ENO2) was associated with short overall survival in ccRCC patients (P=0.023). High mRNA expression of cyclin D1 (CCND1) (P<0.001), fms related tyrosine kinase 1 (FLT1) (P=0.004), plasminogen (PLG) (P<0.001) and von Willebrand factor (VWF) (P=0.008) appeared to serve as favorable factors in survival. These findings indicate that the DEGs may be key genes in ccRCC pathogenesis and five genes, including ENO2, CCND1, PLT1, PLG and VWF, may serve as potential prognostic biomarkers in ccRCC.", "claims": [{"id": "claim-method", "statement": "Survival analysis was performed by Kaplan-Meier method, and the log-rank test was carried out.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:30008862", "locator": "sections[9] \"TCGA verification and survival analysis of hub genes\" paragraph 2", "quote": "Survival analysis was performed by Kaplan-Meier method, and the log-rank test was carried out."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:30008862", "locator": "sections[22] \"Availability of data and materials\" paragraph 2", "quote": "The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Using GEO2R on three Gene Expression Omnibus profiles (GSE36895, GSE46699 and GSE71963), the study identified 229 genes consistently differentially expressed across all three datasets, including 65 upregulated and 164 downregulated genes in ccRCC tissues compared with normal kidney tissues.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:30008862", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "GEO2R was used to identify differentially expressed genes (DEGs) in ccRCC tissues and normal samples."}, {"asset": "source:pmid:30008862", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "Three expression profiles (GSE36895, GSE46699 and GSE71963) were collected from Gene Expression Omnibus."}, {"asset": "source:pmid:30008862", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "A total of 65 up- and 164 downregulated genes were identified as DEGs."}, {"asset": "source:pmid:30008862", "locator": "sections[12] \"Identification of DEGs in ccRCC\" paragraph 2", "quote": "There were 229 genes consistently differentially expressed in all three datasets (Fig. 1), including 65 upregulated DEGs and 164 downregulated DEGs in ccRCC tissues compared with normal kidney tissues (Table I)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Using GEO2R on three Gene Expression Omnibus profiles (GSE36895, GSE46699 and GSE71963), the study identified 229 genes consistently differentially expressed across all three datasets, including 65 upregulated and 164 downregulated genes in ccRCC tissues compared with normal kidney tissues.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:30008862"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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