Prediction and analysis of novel key genes ITGAX, LAPTM5, SERPINE1 in clear cell renal cell carcinoma through bioinformatics analysis.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:33976979", "kind": "science-record", "revision": 7, "content_hash": "sha256:46bde9ca3d4cf92e1384861c6565985553ae009322c3c6e1c79c784b1c930d52", "created_at": "2026-11-01T15:41:35Z", "updated_at": "2026-11-01T22:03:44Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Prediction and analysis of novel key genes ITGAX, LAPTM5, SERPINE1 in clear cell renal cell carcinoma through bioinformatics analysis.", "doi": "10.7717/peerj.11272", "pmid": "33976979", "authors": ["Yingli Sui", "Kun Lu", "Lin Fu"], "journal": "PeerJ", "year": 2021, "abstract": "BACKGROUND: Clear Cell Renal Cell Carcinoma (CCRCC) is the most aggressive subtype of Renal Cell Carcinoma (RCC) with high metastasis and recurrence rates. This study aims to find new potential key genes of CCRCC.\nMETHODS: Four gene expression profiles (GSE12606, GSE53000, GSE68417, and GSE66272) were downloaded from the Gene Expression Omnibus (GEO) database. The TCGA KIRC data was downloaded from The Cancer Genome Atlas (TCGA). Using GEO2R, the differentially expressed genes (DEG) in CCRCC tissues and normal samples were analyzed. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed in DAVID database. A protein-protein interaction (PPI) network was constructed and the hub gene was predicted by STRING and Cytoscape. GEPIA and Kaplan-Meier plotter databases were used for further screening of Key genes. Expression verification and survival analysis of key genes were performed using TCGA database, GEPIA database, and Kaplan-Meier plotter. Receiver operating characteristic (ROC) curve was used to analyze the diagnostic value of key genes in CCRCC, which is plotted by R software based on TCGA database. UALCAN database was used to analyze the relationship between key genes and clinical pathology in CCRCC and the methylation level of the promoter of key genes in CCRCC.\nRESULTS: A total of 289 up-regulated and 449 down-regulated genes were identified based on GSE12606, GSE53000, GSE68417, and GSE66272 profiles in CCRCC. The upregulated DEGs were mainly enriched with protein binding and PI3K-Akt signaling pathway, whereas down-regulated genes were enriched with the integral component of the membrane and metabolic pathways. Next, the top 35 genes were screened out from the PPI network according to Degree, and three new key genes ITGAX, LAPTM5 and SERPINE1 were further screened out through survival and prognosis analysis. Further results showed that the ITGAX, LAPTM5, and SERPINE1 levels in CCRCC tumor tissues were significantly higher than those in normal tissues and were associated with poor prognosis. ROC curve shows that ITGAX, LAPTM5, and SERPINE1 have good diagnostic value with good specificity and sensitivity. The promoter methylation levels of ITGAX, LAPTM5 and SERPINE1 in CCRCC tumor tissues were significantly lower than those in normal tissues. We also found that key genes were associated with clinical pathology in CCRCC.\nCONCLUSION: ITGAX, LAPTM5, and SERPINE1 were identified as novel key candidate genes that could be used as prognostic biomarkers and potential therapeutic targets for CCRCC.", "claims": [{"id": "claim-method", "statement": "Statistically significant differences between the normal tissues group and tumor tissues group were determined using Student’s t tests.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33976979", "locator": "sections[8] \"Statistical analysis\" paragraph 2", "quote": "Statistically significant differences between the normal tissues group and tumor tissues group were determined using Student’s t tests."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The following information was supplied regarding data availability:\nThe raw data and code are available in the Supplemental Files.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33976979", "locator": "sections[28] \"Data Availability Statement\" paragraphs 1-3", "quote": "The following information was supplied regarding data availability:\nThe raw data and code are available in the Supplemental Files."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": null, "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:33976979"], "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:GSE12606"], "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:GSE12606"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:33976979", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.7717/peerj.11272", "sha256": 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"sha256:80410a258a2f5ec5856e2ca45509043c207fb8cba06174639fc2326058462835", "bytes": 705, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[10]/table-wrap[1]#table-1", "version": null, "note": "Summary of TCGA and GEO Clear Cell Renal Cell Carcinoma datasets.", "structure": {"pmcid": "PMC8063882", "section_index": 10, "section_title": "Volcano plots of the differentially expressed genes in four datasets", "row_count": 6, "column_count": 7}, "table": {"label": "Table 1", "caption": "Summary of TCGA and GEO Clear Cell Renal Cell Carcinoma datasets.", "rows": [["Author, year", "Sample", "GEO no.", "Platform", "Normal", "Tumor", "(Refs.)"], ["Stickel JS et al, 2009", "CCRCC", "GSE12606", "GPL570", "3", "3", "Stickel et al. (2009)"], ["Gerlinger M et al, 2014", "CCRCC", "GSE53000", "GPL6244", "6", "54", "Gerlinger et al. (2014)"], ["Thibodeau BJ et al, 2016", "CCRCC", "GSE68417", "GPL6244", "29", "14", "Thibodeau et al. (2016)"], ["Wotschofsky Z et al, 2016", "CCRCC", "GSE66272", "GPL5029", "27", "26", "Wotschofsky et al. (2016)"], ["TCGA", "CCRCC", "–", "–", "72", "539", ""]], "row_count": 6, "column_count": 7, "numeric_cells": 26, "header_rows": 1, "locator": "section[10]/table-wrap[1]#table-1"}}, {"id": "asset:table:pmid:33976979:2", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:e7a52f5ab666369e0bc2f7e7e3045c46e37081b7a2a648585a15a9d156ae522e", "bytes": 5835, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[11]/table-wrap[1]#table-2", "version": null, "note": "GO and KEGG analysis of differentially expressed DEG associated with CCRCC.", "structure": {"pmcid": "PMC8063882", "section_index": 11, "section_title": "GO and KEGG enrichment analysis of DEGs", "row_count": 81, "column_count": 5}, "table": {"label": "Table 2", "caption": "GO and KEGG analysis of differentially expressed DEG associated with CCRCC.", "rows": [["Expression", "Category", "Term", "Count", "P-value"], ["Upregulated", "GO_BP", "GO:0006954∼inflammatory response", "30", "1.30E−12"], ["", "GO_BP", "GO:0007165∼signal transduction", "29", "1.31E−02"], ["", "GO_BP", "GO:0007155∼cell adhesion", "26", "5.33E−08"], ["", "GO_BP", "GO:0006955∼immune response", "24", "1.76E−07"], ["", "GO_BP", "GO:0042493∼response to drug", "21", "5.92E−08"], ["", "GO_BP", "GO:0045087∼innate immune response", "19", "1.36E−04"], ["", "GO_BP", "GO:0030198∼extracellular matrix organization", "18", "1.08E−08"], ["", "GO_BP", "GO:0050900∼leukocyte migration", "17", "6.55E−11"], ["", "GO_BP", "GO:0001525∼angiogenesis", "17", "4.06E−07"], ["", "GO_BP", "GO:0008284∼positive regulation of cell proliferation", "17", "2.57E−03"], ["", "GO_CC", "GO:0005886∼plasma membrane", "108", "1.13E−09"], ["", "GO_CC", "GO:0016021∼integral component of membrane", "107", "2.03E−04"], ["", "GO_CC", "GO:0070062∼extracellular exosome", "66", "2.68E−04"], ["", "GO_CC", "GO:0016020∼membrane", "64", "4.11E−07"], ["", "GO_CC", "GO:0005887∼integral component of plasma membrane", "62", "6.07E−14"], ["", "GO_CC", "GO:0005576∼extracellular region", "50", "1.98E−06"], ["", "GO_CC", "GO:0005615∼extracellular space", "49", "2.48E−08"], ["", "GO_CC", "GO:0009986∼cell surface", "31", "1.08E−09"], ["", "GO_CC", "GO:0005783∼endoplasmic reticulum", "20", "4.86E−02"], ["", "GO_CC", "GO:0000139∼Golgi membrane", "17", "1.94E−02"], ["", "GO_MF", "GO:0005515∼protein binding", "154", "6.05E−03"], ["", "GO_MF", "GO:0005524∼ATP binding", "36", "6.15E−03"], ["", "GO_MF", "GO:0042803∼protein homodimerization activity", "21", "7.66E−03"], ["", "GO_MF", "GO:0042802∼identical protein binding", "20", "1.92E−02"], ["", "GO_MF", "GO:0005102∼receptor binding", "19", "7.41E−06"], ["", "GO_MF", "GO:0004872∼receptor activity", "14", "2.70E−05"], ["", "GO_MF", "GO:0004672∼protein kinase activity", "12", "2.09E−02"], ["", "GO_MF", "GO:0005215∼transporter activity", "8", "3.41E−02"], ["", "GO_MF", "GO:0004888∼transmembrane signaling receptor activity", "8", "4.43E−02"], ["", "GO_MF", "GO:0005201∼extracellular matrix structural constituent", "7", "5.17E−04"], ["", "KEGG", "hsa04151: PI3K-Akt signaling pathway", "19", "2.01E−04"], ["", "KEGG", "hsa04510: Focal adhesion", "17", "3.76E−06"], ["", "KEGG", "hsa05200: Pathways in cancer", "17", "5.96E−03"], ["", "KEGG", "hsa04066: HIF-1 signaling pathway", "12", "3.37E−06"], ["", "KEGG", "hsa04015: Rap1 signaling pathway", "12", "3.56E−03"], ["", "KEGG", "hsa04145: Phagosome", "10", "3.39E−03"], ["", "KEGG", "hsa05205: Proteoglycans in cancer", "10", "2.05E−02"], ["", "KEGG", "hsa05150: Staphylococcus aureus infection", "9", "1.14E−05"], ["", "KEGG", "hsa04611: Platelet activation", "9", "4.86E−03"], ["", "KEGG", "hsa05133: Pertussis", "8", "7.79E−04"], ["Downregulated", "GO_BP", "GO:0055114∼oxidation–reduction process", "33", "3.33E−05"], ["", "GO_BP", "GO:0034220∼ion transmembrane transport", "19", "5.29E−06"], ["", "GO_BP", "GO:0042493∼response to drug", "18", "1.62E−03"], ["", "GO_BP", "GO:0006811∼ion transport", "14", "1.66E−05"], ["", "GO_BP", "GO:0055085∼transmembrane transport", "14", "8.16E−03"], ["", "GO_BP", "GO:0007588∼excretion", "13", "4.97E−11"], ["", "GO_BP", "GO:0010628∼positive regulation of gene expression", "13", "3.13E−02"], ["", "GO_BP", "GO:0006814∼sodium ion transport", "12", "4.94E−06"], ["", "GO_BP", "GO:0001822∼kidney development", "12", "8.92E−06"], ["", "GO_BP", "GO:0008152∼metabolic process", "12", "3.22E−03"], ["", "GO_CC", "GO:0016021∼integral component of membrane", "171", "4.63E−07"], ["", "GO_CC", "GO:0070062∼extracellular exosome", "170", "1.01E−33"], ["", "GO_CC", "GO:0005886∼plasma membrane", "162", "2.99E−12"], ["", "GO_CC", "GO:0005887∼integral component of plasma membrane", "76", "3.16E−11"], ["", "GO_CC", "GO:0005615∼extracellular space", "50", "1.87E−03"], ["", "GO_CC", "GO:0016324∼apical plasma membrane", "44", "4.39E−22"], ["", "GO_CC", "GO:0016323∼basolateral plasma membrane", "28", "2.05E−14"], ["", "GO_CC", "GO:0009986∼cell surface", "24", "5.53E−03"], ["", "GO_CC", "GO:0005759∼mitochondrial matrix", "19", "8.74E−04"], ["", "GO_CC", "GO:0043025∼neuronal cell body", "15", "1.88E−02"], ["", "GO_MF", "GO:0042803∼protein homodimerization activity", "33", "7.43E−04"], ["", "GO_MF", "GO:0005509∼calcium ion binding", "29", "7.77E−03"], ["", "GO_MF", "GO:0043565∼sequence-specific DNA binding", "20", "4.43E−02"], ["", "GO_MF", "GO:0016491∼oxidoreductase activity", "13", "3.24E−03"], ["", "GO_MF", "GO:0046983∼protein dimerization activity", "11", "3.31E−03"], ["", "GO_MF", "GO:0008201∼heparin binding", "11", "5.22E−03"], ["", "GO_MF", "GO:0005088∼Ras guanyl-nucleotide exchange factor activity", "10", "1.78E−03"], ["", "GO_MF", "GO:0003824∼catalytic activity", "10", "3.74E−02"], ["", "GO_MF", "GO:0016787∼hydrolase activity", "10", "4.07E−02"], ["", "GO_MF", "GO:0046934∼phosphatidylinositol-4,5-bisphosphate 3-kinase activity", "9", "1.10E−04"], ["", "KEGG", "hsa01100: Metabolic pathways", "68", 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