Identification of Key Genes and Pathways in Tongue Squamous Cell Carcinoma Using Bioinformatics Analysis.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:29240723", "kind": "science-record", "revision": 8, "content_hash": "sha256:adbbd2e22ea9e5fac252ab1ec2bbd0b2e3e2592fd2b7f91271aca6659fef5c71", "created_at": "2026-11-01T15:40:30Z", "updated_at": "2026-11-01T21:59:37Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification of Key Genes and Pathways in Tongue Squamous Cell Carcinoma Using Bioinformatics Analysis.", "doi": "10.12659/msm.905035", "pmid": "29240723", "authors": ["Huayong Zhang", "Jianmin Liu", "Xiaoyan Fu", "Ankui Yang"], "journal": "Medical science monitor : international medical journal of experimental and clinical research", "year": 2017, "abstract": "BACKGROUND Tongue squamous cell carcinoma (TSCC) is a major type of oral cancers and has remained an intractable cancer over the past decades. The aim of this study was to identify differentially expressed genes (DEGs) during TSCC and reveal their potential mechanisms. MATERIAL AND METHODS The gene expression profiles of GSE13601 were downloaded from the GEO database. The GSE13601 dataset contains 57 samples, including 31 tongue SCC samples and 26 matched normal mucosa samples. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) enrichment analyses were performed; Cytoscape software was used for the protein-protein interaction (PPI) network and module analysis of the DEGs. RESULTS We identified a total of 1,050 upregulated DEGs (uDEGs) and 702 downregulated DEGs (dDEGs) of TSCC. The GO analysis results showed that uDEGs were significantly enriched in the following biological processes (BP): signal transduction, positive or negative regulation of cell proliferation, and negative regulation of cell proliferation. The dDEGs were significantly enriched in the following biological processes: signal transduction, cell adhesion, and apoptotic process. The KEGG pathway analysis showed that uDEGs were enriched in metabolic pathways, pathways in cancer, and PI3K-Akt signaling pathway, while the dDEGs were enriched in focal adhesion and ECM-receptor interaction. The top centrality hub genes RAC1, APP, EGFR, KNG1, AGT, and HRAS were identified from the PPI network. Module analysis revealed that TSCC was associated with significant pathways, including neuroactive ligand-receptor interaction, calcium signaling pathway, and chemokine signaling pathway. CONCLUSIONS The present study identified key genes and signal pathways, which deepen our understanding of the molecular mechanisms of carcinogenesis and development of the disease, and might be used as diagnostic and therapeutic molecular biomarkers for TSCC.", "claims": [{"id": "claim-method", "statement": "The adjusted p values (adj. p) were applied to correct the false positive results by default Benjamini-Hochberg false discovery rate method.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:29240723", "locator": "sections[4] \"Data processing\" paragraph 2", "quote": "The adjusted p values (adj. p) were applied to correct the false positive results by default Benjamini-Hochberg false discovery rate method."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The Gene Expression Omnibus (GEO, http://www.ncbi.nlm.nih.gov/geo) is a public functional genomics data repository including array- and sequence-based data, and is freely available for users. The gene expression profiles of GSE13601 were obtained from the GEO database. The GSE13601 dataset has 57 samples, including 31 TSCC samples and 26 matched normal mucosa samples.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:29240723", "locator": "sections[3] \"Datasets\" paragraph 2", "quote": "The Gene Expression Omnibus (GEO, http://www.ncbi.nlm.nih.gov/geo) is a public functional genomics data repository including array- and sequence-based data, and is freely available for users."}, {"asset": "source:pmid:29240723", "locator": "sections[3] \"Datasets\" paragraph 2", "quote": "The gene expression profiles of GSE13601 were obtained from the GEO database."}, {"asset": "source:pmid:29240723", "locator": "sections[3] \"Datasets\" paragraph 2", "quote": "The GSE13601 dataset has 57 samples, including 31 TSCC samples and 26 matched normal mucosa samples."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Using GEO2R on GSE13601 downloaded from the GEO database, with adj. p<0.01 and |log2FC|>1 as the statistical criteria, the study identified 1,752 DEGs in TSCC tissues versus normal tissues: 1,050 upregulated and 702 downregulated.", "kind": "quantitative", "target": {"value": 0.01, "unit": "p-value", "tolerance": null, "source": "Based on the GEO2R analysis, using the adj. p<0.01 and |log2FC|>1 criteria, a total of 1,752 DEGs were identified, consisting of 1,050 upregulated DEGs (uDEGs) and 702 downregulated DEGs (dDEGs) in TSCC tissues compared with normal tissues."}, "evidence": [{"asset": "source:pmid:29240723", "locator": "sections[0] \"Abstract\" paragraph 2", "quote": "The gene expression profiles of GSE13601 were downloaded from the GEO database."}, {"asset": "source:pmid:29240723", "locator": "sections[9] \"Identification of DEGs\" paragraph 2", "quote": "Based on the GEO2R analysis, using the adj. p<0.01 and |log2FC|>1 criteria, a total of 1,752 DEGs were identified, consisting of 1,050 upregulated DEGs (uDEGs) and 702 downregulated DEGs (dDEGs) in TSCC tissues compared with normal tissues."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Using GEO2R on GSE13601 downloaded from the GEO database, with adj. p<0.01 and |log2FC|>1 as the statistical criteria, the study identified 1,752 DEGs in TSCC tissues versus normal tissues: 1,050 upregulated and 702 downregulated.", "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:29240723"], "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:GSE13601"], "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:GSE13601"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:29240723", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.12659/msm.905035", "sha256": "sha256:1a365ae83a3390538c4a2005dc9366cab407b2e9143031c549ca20e450c485e8", "bytes": 34796, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.12659/msm.905035", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC5738838", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE13601", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE13601", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE13601", "version": null, "note": "The Gene Expression Omnibus (GEO, http://www.ncbi.nlm.nih.gov/geo) is a public functional genomics data repository including array- and sequence-based data, and is freely available for users. 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null, "platform": "8300", "taxon": "Homo sapiens", "title": "Oral tongue cancer gene expression profiling: Identification of novel potential prognosticators", "resolution_checked_at": "2026-11-01T15:39:54Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "asset:table:pmid:29240723:1", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:a8f1e1d95c9ec25d7573f161b26699a80dd93609e337426ddca307e82a853a49", "bytes": 2846, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[10]/table-wrap[1]#t1-medscimonit-23-5924", "version": null, "note": "Gene ontology analysis of differentially expressed genes associated with TSCC.", "structure": {"pmcid": "PMC5738838", "section_index": 10, "section_title": "GO term enrichment analysis", "row_count": 31, "column_count": 6}, "table": {"label": "Table 1", "caption": "Gene ontology analysis of differentially expressed genes associated with TSCC.", "rows": [["Expression", "Category", "Term/gene function", "Gene count", "%", "P value"], ["Up-regulated", "GOTERM_BP_DIRECT", "GO: 0007165~signal transduction", "95", "9.59", "8.67E-05"], ["GOTERM_BP_DIRECT", "GO: 0045944~positive regulation of transcription from RNA polymerase II promoter", "82", "8.27", "1.72E-04"], ["GOTERM_BP_DIRECT", "GO: 0000122~negative regulation of transcription from RNA polymerase II promoter", "60", "6.05", "0.002"], ["GOTERM_BP_DIRECT", "GO: 0008285~negative regulation of cell proliferation", "45", "4.54", "1.50E-05"], ["GOTERM_BP_DIRECT", "GO: 0007155~cell adhesion", "45", "4.54", "2.35E-04"], ["GOTERM_CC_DIRECT", "GO: 0005886~plasma membrane", "263", "26.54", "6.71E-05"], ["GOTERM_CC_DIRECT", "GO: 0005829~cytosol", "223", "22.50", "8.89E-05"], ["GOTERM_CC_DIRECT", "GO: 0070062~extracellular exosome", "215", "21.70", "1.05E-09"], ["GOTERM_CC_DIRECT", "GO: 0005576~extracellular region", "141", "14.23", "5.09E-10"], ["GOTERM_CC_DIRECT", "GO: 0005615~extracellular space", "134", "13.52", "5.39E-13"], ["GOTERM_MF_DIRECT", "GO: 0005515~protein binding", "372", "37.53", "0.004"], ["GOTERM_MF_DIRECT", "GO: 0005524~ATP binding", "106", "10.70", "0.003"], ["GOTERM_MF_DIRECT", "GO: 0005509~calcium ion binding", "77", "7.77", "1.41E-08"], ["GOTERM_MF_DIRECT", "GO: 0042803~protein homodimerization activity", "66", "6.66", "5.29E-05"], ["GOTERM_MF_DIRECT", "GO: 0003700~transcription factor activity, sequence-specific DNA binding", "64", "6.46", "0.003"], ["Down-regulated", "GOTERM_BP_DIRECT", "GO: 0007165~signal transduction", "83", "12.56", "6.42E-08"], ["GOTERM_BP_DIRECT", "GO: 0007155~cell adhesion", "57", "8.62", "1.90E-14"], ["GOTERM_BP_DIRECT", "GO: 0006915~apoptotic process", "47", "7.11", "1.69E-06"], ["GOTERM_BP_DIRECT", "GO: 0008284~positive regulation of cell proliferation", "44", "6.66", "2.66E-07"], ["GOTERM_BP_DIRECT", "GO: 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"reader": "read_table", "reader_status": "available", "identifier": "section[12]/table-wrap[1]#t3-medscimonit-23-5924", "version": null, "note": "The top 10 differentially expressed genes with higher scores, respectively, identified by the three centrality methods.", "structure": {"pmcid": "PMC5738838", "section_index": 12, "section_title": "PPI network construction and modules selection", "row_count": 11, "column_count": 6}, "table": {"label": "Table 3", "caption": "The top 10 differentially expressed genes with higher scores, respectively, identified by the three centrality methods.", "rows": [["Subgraph", "Degree", "Closeness"], ["APP", "7.93E10", "RAC1", "78.0", "RAC1", "0.01866"], ["KNG1", "7.47E10", "APP", "74.0", "EGFR", "0.01864"], ["AGT", "7.20E10", "EGFR", "59.0", "HRAS", "0.01863"], ["RGS19", "4.86E10", "KNG1", "58.0", "BCL2", "0.01861"], ["GNAI1", "3.64E10", "CDK1", "56.0", "CDC42", "0.01860"], ["GCG", "3.51E10", "AGT", "55.0", "HIF1A", "0.01860"], ["ADCY8", "3.27E10", "HRAS", "55.0", "PRKCA", "0.01860"], ["ADCY1", "3.03E10", "CDC42", "55.0", "CDKN1A", "0.01859"], ["CXCL12", "2.97E10", "ADCY8", "54.0", "MMP9", "0.01859"], ["GNA15", "2.74E10", "GCG", "50.0", "MAX", "0.01858"]], "row_count": 11, "column_count": 6, "numeric_cells": 35, "header_rows": 1, "locator": "section[12]/table-wrap[1]#t3-medscimonit-23-5924"}}, {"id": "asset:table:pmid:29240723:4", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:296d11c2e64e033d862cde42723276549cb69d7f935e3310c3ac0b75773e0422", "bytes": 1018, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[12]/table-wrap[2]#t4-medscimonit-23-5924", "version": null, "note": "GO and pathway analysis of genes in selected module.", "structure": {"pmcid": "PMC5738838", "section_index": 12, "section_title": "PPI network construction and modules selection", "row_count": 13, "column_count": 5}, "table": {"label": "Table 4", "caption": "GO and pathway analysis of genes in selected module.", "rows": [["Category", "Pathway ID", "Term/gene and function", "Count", "P-value"], ["KEGG_PATHWAY", "hsa4080", "Neuroactive ligand-receptor interaction", "16", "2.83E-17"], ["hsa4020", "Calcium signaling pathway", "12", "1.50E-13"], ["hsa4062", "Chemokine signaling pathway", "12", "1.50E-13"], ["GOTERM_BP_DIRECT", "GO.0007165", "Signal transduction", "31", "1.74E-10"], ["GO.0044700", "Single organism signaling", "29", "3.40E-08"], ["GO.0007154", "Cell communication", "29", "5.69E-08"], ["GOTERM_CC_DIRECT", "GO.0005886", "Plasma membrane", "28", "1.20E-07"], ["GO.0071944", "Cell periphery", "28", "1.38E-07"], ["GO.0044459", "Plasma membrane part", "21", "1.20E-07"], ["GOTERM_MF_DIRECT", "GO.0005515", "Protein binding", "20", "0.0176"], ["GO.0005102", "Receptor binding", "19", "7.39E-11"], ["GO.0004871", "Signal transducer activity", "16", "5.68E-06"]], "row_count": 13, "column_count": 5, 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A run that reproduces the effect is judged against this threshold."}], "gaps": ["method.reader_named_unmapped"]}, "capability": {"state": "complete", "requirements": [{"capability_id": "capability:computational_analysis", "label": "Computational analysis platform", "assay_families": ["meta_analysis", "machine_learning", "survival_analysis", "statistical_regression", "pca", "molecular_docking", "network_analysis", "differential_expression", "gwas"], "availability_state": "owned", "tier_unlocked": "R1", "candidate": "Automated Assays Laravel application and simulated adapters"}], "gaps": []}, "readiness": {"state": "complete", "tier": "R1", "blocking_axis": "none", "blocked_on": "nothing:replicable_now", "axes": {"method": {"tier": "R1", "expressible": true, "required_operations": ["build_graph", "centrality_scores", "pathway_enrich"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: ppi_network."}, "capability": {"tier": "R1", "capability_id": "capability:computational_analysis", "availability_state": "owned", "basis": "The computational analysis is owned. 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