Key genes associated with prognosis and metastasis of clear cell renal cell carcinoma.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:35036081", "kind": "science-record", "revision": 4, "content_hash": "sha256:b4545d3eaa4aa14df345782945fc7657688816ba9e73ab1a866f2333d8fc7c55", "created_at": "2026-11-01T17:36:45Z", "updated_at": "2026-11-01T22:05:35Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Key genes associated with prognosis and metastasis of clear cell renal cell carcinoma.", "doi": "10.7717/peerj.12493", "pmid": "35036081", "authors": ["Tingting Zhong", "Zeying Jiang", "Xiangdong Wang", "Honglei Wang", "Meiyi Song", "Wenfang Chen", "Shicong Yang"], "journal": "PeerJ", "year": 2022, "abstract": "BACKGROUND: Clear 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.\nMETHODS: Differentially 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).\nRESULTS: A 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.\nCONCLUSION: PCOLCE, P4HB, COL6A2 and COL6A3 are upregulated in metastatic ccRCC and might be related to poor prognosis and distant metastases.", "claims": [{"id": "claim-method", "statement": "GEO2R (http://www.ncbi.nlm.nih.gov/geo/geo2r), an interactive web tool for DEG analysis of GEO series across experimental conditions, was used to analyze the DEGs between primary ccRCC and metastatic ccRCC in the three datasets.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35036081", "locator": "sections[4] \"Identification of DEGs\" paragraph 2", "quote": "GEO2R (http://www.ncbi.nlm.nih.gov/geo/geo2r), an interactive web tool for DEG analysis of GEO series across experimental conditions, was used to analyze the DEGs between primary ccRCC and metastatic ccRCC in the three datasets."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The raw measurements are available in the Supplementary File.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35036081", "locator": "sections[24] \"Data Availability\" paragraph 2", "quote": "The raw measurements are available in the Supplementary File."}], "state": "complete"}, {"id": "claim-target-result", "statement": "A total of 104 co-expressed DEGs were identified in the three datasets.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:35036081", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "A total of 104 co-expressed DEGs were identified in the three datasets."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "A total of 104 co-expressed DEGs were identified in the three datasets.", "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:35036081"], "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. This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE105288"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "complete", "blocked_on": null, "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE105288"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:35036081", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.7717/peerj.12493", "sha256": 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Immunohistochemistry revealed higher expression of the proteins e", "zed with unpaired t-test, and the results of immunohistochemistry quantification were analyzed with paired t-t", "rmation 3Raw dataqRT-PCR & semi-quantitative immunohistochemistry results10.7717/peerj.12493/supp-3Click here"], "order_basis": "paper_text_order:1888", "id": "assay:1"}, {"role": "data_generation", "definition_id": "cell_culture", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.77, "evidence": ["the BIOWING company in Shanghai. 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