{"data":{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:30186410", "kind": "science-record", "revision": 5, "content_hash": "sha256:a2d6c10f65e6e7e3c42fa4356d0249ab59d50be490608738d6beb29c11fd1606", "created_at": "2026-11-01T15:40:37Z", "updated_at": "2026-11-01T22:00:01Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification of key pathways and biomarkers in sorafenib-resistant hepatocellular carcinoma using bioinformatics analysis.", "doi": "10.3892/etm.2018.6427", "pmid": "30186410", "authors": ["Danping Huang", "Weiqu Yuan", "Hanmin Li", "Shaodong Li", "Zuanguang Chen", "Hongzhi Yang"], "journal": "Experimental and therapeutic medicine", "year": 2018, "abstract": "Hepatocellular carcinoma (HCC) is one of the most common malignant types of cancer, with a high mortality rate. Sorafenib is the sole approved oral clinical therapy against advanced HCC. However, individual patients exhibit varying responses to sorafenib and the development of sorafenib resistance has been a new challenge for its clinical efficacy. The current study identified gene biomarkers and key pathways in sorafenib-resistant HCC using bioinformatics analysis. Gene dataset GSE73571 was obtained from the Gene Expression Omnibus (GEO) database, including four sorafenib-acquired resistant and three sorafenib-sensitive HCC phenotypes. Differentially expressed genes (DEGs) were identified using the web tool GEO2R. Functional and pathway enrichment of DEGs were analyzed using the Database for Annotation, Visualization and Integrated Discovery and the protein-protein interaction (PPI) network was constructed using the Search Tool for the Retrieval of Interacting Genes/Proteins and Cytoscape. A total of 1,319 DEGs were selected, which included 593 upregulated and 726 downregulated genes. Functional and pathway enrichment analysis revealed DEGs enriched in negative regulation of endopeptidase activity, cholesterol homeostasis, DNA replication and repair, coagulation cascades, insulin resistance, RNA transport, cell cycle and others. Eight hub genes, including kininogen 1, vascular cell adhesion molecule 1, apolipoprotein C3, alpha 2-HS glycoprotein, erb-b2 receptor tyrosine kinase 2, secreted protein acidic and cysteine rich, vitronectin and vimentin were identified from the PPI network. In conclusion, the present study identified DEGs and key genes in sorafenib-resistant HCC, which further the knowledge of potential mechanisms in the development of sorafenib resistance and may provide potential targets for early diagnosis and new treatments for sorafenib-resistant HCC.", "claims": [{"id": "claim-method", "statement": "DEGs in resistant and sensitive samples were analyzed by GEO2R. |log2FC|≥0.4 and P<0.01 were used as cut-off criteria and defined a statistically significant difference", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:30186410", "locator": "sections[5] \"DEG analysis\" paragraph 2", "quote": "DEGs in resistant and sensitive samples were analyzed by GEO2R. |log2FC|≥0.4 and P<0.01 were used as cut-off criteria and defined a statistically significant difference"}], "state": "complete"}, {"id": "claim-data-access", "statement": "Data and materials have been provided as part of the submitted article.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:30186410", "locator": "sections[17] \"Availability of data and materials\" paragraph 2", "quote": "Data and materials have been provided as part of the submitted article."}], "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:30186410"], "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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"GO:0005814/centriole", "16", "2.925", "<0.001"], ["GOTERM_BP_DIRECT", "GO:0006260/DNA replication", "25", "4.570", "<0.001"], ["GOTERM_BP_DIRECT", "GO:0006281/DNA repair", "27", "4.936", "<0.001"], ["GOTERM_BP_DIRECT", "GO:0000732/strand displacement", "10", "1.828", "<0.001"], ["GOTERM_BP_DIRECT", "GO:0000731/DNA synthesis involved in DNA repair", "11", "2.011", "<0.001"], ["GOTERM_BP_DIRECT", "GO:0006974/cellular response to DNA damage stimulus", "23", "4.205", "<0.001"]], "row_count": 40, "column_count": 5, "numeric_cells": 120, "header_rows": 3, "locator": "section[11]/table-wrap[1]#tI-etm-0-0-6427"}}, {"id": "asset:table:pmid:30186410:2", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:a0602d9ed6dbeb3e4d47bea2c7d0aa6ea37083a34f7bb912a2856a2e51277861", "bytes": 2302, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[12]/table-wrap[1]#tII-etm-0-0-6427", "version": null, "note": "KEGG pathway analysis of upregulated and downregulated genes in sorafenib-resistant hepatocellular carcinoma.", "structure": {"pmcid": "PMC6122189", "section_index": 12, "section_title": "KEGG pathway analysis", "row_count": 18, "column_count": 5}, "table": {"label": "Table II.", "caption": "KEGG pathway analysis of upregulated and downregulated genes in sorafenib-resistant hepatocellular carcinoma.", "rows": [["A, Upregulated genes"], [""], ["Name", "Gene count", "%", "P-value", "Genes"], ["hsa04610: Complement and coagulation cascades", "20", "2.999", "<0.001", "KNG1, F12, F10, CFB, C3, C1R, SERPING1, F7, C1S, C8B, FGG, FGB, SERPINF2, KLKB1, SERPINA5, SERPIND1, C2, CFI, PLAU, F2R"], ["hsa04142: Lysosome", "14", "2.099", "0.003047", "TCIRG1, CTSZ, CLTB, ACP5, ACP2, CTSA, CTSS, CTSL, LAPTM5, TPP1, ARSA, CTSE, SMPD1, CTSD"], ["hsa04931: Insulin resistance", "13", "1.949", "0.003298", "SREBF1, NR1H2, PPP1R3C, PPP1R3B, SOCS3, SLC2A2, PRKAG2, PRKAB2, NFKBIA, CREB3L3, SLC27A3, CPT1A, PCK1"], ["hsa01100: Metabolic pathways", "74", "11.094", "0.006009", "TM7SF2, ALAD, OGDHL, ADH1C, ADH1A, AGXT, CKB, PTGIS, P4HA2, ST3GAL5, MAT1A, RGN, DAO, ITPK1, AGPAT3, AGPAT2, GATM, ACADS, SPTLC3, FAXDC2, PISD, PNPLA3, PMM1, ALDH3B1, DGAT2, CYP27A1, HAO2, EXT1, AOC1, AKR1D1, LCT, AOC3, ACAA1, GALNT2, ENPP7, ASS1, HSD17B2, ALDOC, ENPP3, CERS4, PLPP3, PIPOX, THTPA, B3GNT5, DHCR7, PLA2G12B, PEMT, HAAO, ENO3, ETNK2, FUT2, BDH1, GAL3ST1, ACSL5, CYP19A1, TCIRG1, MOGAT3, ST6GAL1, NDUFA2, SI, MAOB, HOGA1, AMPD3, IDNK, PCK1, POLD4, BAAT, HMGCS2, SMPD1, LIPC, PHYKPL, PON3"], ["hsa04975: Fat digestion and absorption", "7", "1.049", "0.007472", "APOA4, ABCG8, MOGAT3, DGAT2, PLA2G12B, PLPP3, AGPAT2"], [""], ["B, Downregulated genes"], [""], ["Name", "Gene count", "%", "P-value", "Genes"], [""], ["hsa03008: Ribosome biogenesis in eukaryotes", "17", "3.108", "<0.001", "XPO1, GTPBP4, UTP6, UTP15, GNL3L, BMS1, DROSHA, WDR36, POP1, WDR3, NOP58, GNL2, MDN1, RBM28, SPATA5, WDR43, GNL3"], ["hsa03013: RNA transport", "17", "3.108", "<0.001", "XPOT, XPO1, XPO5, ALYREF, EIF5B, NUPL2, NUP155, PNN, TRNT1, UPF3B, SEH1L, NUP205, POP1, EIF3J, RANBP2, TPR, GEMIN5"], ["hsa03460: Fanconi anemia pathway", "9", "1.645", "<0.001", "FANCM, BLM, FANCD2, FANCI, BRCA2, BRIP1, ATR, FANCA, BRCA1"], ["hsa04742: Taste transduction", "7", "1.280", "<0.001", "TAS2R13, TAS2R14, TAS2R19, TAS2R46, TAS2R43, TAS2R20, TAS2R10"], ["hsa04110: Cell cycle", "9", "1.645", "0.014438", "CDC7, CDC6, RBL1, PRKDC, ATR, MYC, CDC25A, ATM, STAG1"]], "row_count": 18, "column_count": 5, "numeric_cells": 48, "header_rows": 3, "locator": "section[12]/table-wrap[1]#tII-etm-0-0-6427"}}], "gaps": ["asset:data:geo:GSE73571 not downloaded", "asset:data:geo:GSE73571 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "family": "network_analysis", "specific": "ppi_network", "label": "Network / pathway analysis", "dsl_operations": 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Records without an assay match currently receive a zero-hour model value.","status":"unverified","severity":"high"},{"code":"signal_score_without_citations","basis":["5,529 of 5,529 records (100.0%) have no citation count from the source metadata."],"claim":"Signal score","gloss":"The signal score uses publication-type weight because the mirror supplied zero citation counts.","detail":"The source supplied no citation counts for any record in this run, so the signal score is publication-type weight only. The citation term of the ranking is inert here, and the shortlist is ordered by publication type alone.","status":"unverified","severity":"high"},{"code":"abstract_absent","basis":["1,667 of 5,529 records (30.2%) carry no abstract at all."],"claim":"Evidence base for classification","gloss":"Some records contain a title and publication type only, defining the available classification evidence.","detail":"Where the mirror contains a title and publication types only, those fields define the classifier evidence. A methods section is required for fuller automated and human review.","status":"unverified","severity":"medium"},{"code":"classifier_agreement_measured","basis":["Published two-way decision agreement 77.7% (310 of 399 decidable records) from a stratified hand-check of 438 real records.","Three-way diagnostic agreement 73.9% (288 of 390 decidable records).","data_only agreement 75.2% (100 of 133 decidable).","48 record(s) could not be decided from title and abstract and were excluded from the denominator.","56 analysis-only records were published under another work type, so the data_only share is not an upper bound."],"claim":"Published automatable decision","gloss":"This figure has been checked against a human reading the same papers, so we know how often it is right.","detail":"The published automatable / not-automatable distribution comes from a rule-based classifier that was hand-checked against a fixed ground-truth definition. The agreement rates below are measured, not estimated. The three-way work type remains a diagnostic and is reported separately.","status":"measured","severity":"high"},{"code":"llm_comparison_not_measured","basis":["rule_based_v1+lex99e1195c7d6f produced 5,529 of 5,529 classifications.","Measured on 438 labelled records; these are RULE-BASED figures, not model results."],"claim":"Rule-based versus LLM agreement","gloss":"Every number here is the rule engine’s own. Model comparison begins when a working API credential is connected and measured.","detail":"The published two-way decision agreed with a human reading on 310 of 399 decidable records (77.7%). The diagnostic three-way label agreed on 288 of 390 decidable records (73.9%). Every percentage in this run belongs to the rule engine. Model comparison begins when a working API credential is connected and measured.","status":"not_measured","severity":"high"},{"code":"confidence_is_a_band","basis":["low band: 135 of 210 hand-judged records were correct, 64.3% [57.6, 70.5] (95% CI).","medium band: 80 of 104 hand-judged records were correct, 76.9% [68.0, 84.0] (95% CI).","high band: 73 of 76 hand-judged records were correct, 96.0% [89.0, 98.7] (95% CI).","A fitted calibrated probability was built, measured and withdrawn: it overstated held-out accuracy and reorders nothing."],"claim":"Confidence band and evidence score","gloss":"The confidence band carries a measured accuracy interval; 0.85 represents relative rank strength.","detail":"Confidence on this run is a BAND plus its measured accuracy interval. The number stored alongside each record is a monotone evidence score that orders records; 0.85 represents relative rank strength. A fitted probability was withdrawn after it overstated held-out accuracy. Threshold on the band.","status":"measured","severity":"medium"},{"code":"three_way_split_is_diagnostic","basis":["The corpus is published at the two-way decision: automatable or not-automatable. The three-way split (data_only / physical / mixed) is published as a diagnostic with its measured reliability attached, not as a claim, because the rule engine's `mixed` call cannot be defended.","The engine called 22 record(s) mixed; 10 matched the human judgement (45.5%, 95% CI 26.9-65.3).","The engine's `mixed` call is right on 10/22 hand-judged records (45.5%, 95% CI 26.9%-65.3%); a constant `physical` guess scores 36.4%.","The engine's `mixed` call does not reliably beat a constant `physical` guess on the hand-judged records it labels mixed.","The sign of that difference flips between two independent samples, so the three-way refinement is not demonstrably informative.","The mixed stratum contributes a disproportionate share of errors relative to its size.","At title-only depth the physical/mixed split collapses: a title says that work was done, not whether it was also analysed."],"claim":"The published decision is two-way","gloss":"The three-way split is shown for diagnosis only. The published split is two ways.","detail":"Count and filter the corpus on automatable versus not-automatable. The data_only / physical / mixed split remains an internal engine diagnostic because the mixed call has lower measured reliability.","status":"measured","severity":"medium"},{"code":"automatable_flag_unproven","basis":["6 of 29 assay families are marked automatable now: meta_analysis, machine_learning, survival_analysis, pca, molecular_docking, differential_expression.","The flag is a rule over assay family and work type; validation begins with the first executed replication.","It inherits the 75.2% data_only agreement rate, because the flag requires the record to be analysis-only."],"claim":"Automatable now","gloss":"This flag marks assay families the rules classify as data-only. The first executed replication will validate it.","detail":"This flag marks families the rules consider replicable from data alone. Its validity depends on the analysis-only classification and will be measured through an executed replication.","status":"unverified","severity":"medium"}],"confidence_policy":"band_with_measured_interval","confidence_contract":{"policy":"band_with_measured_interval","summary":"Confidence is reported as a BAND with a measured accuracy interval. The raw evidence score supplies monotone ordering. A fitted point estimate was withdrawn after it overstated held-out accuracy.","evidence_score":"A monotone evidence score in [0,1] built from cue mass, axis separation and text coverage. Use it to order records. Interpret 0.85 as relative rank strength.","confidence_band":"low | medium | high. Consumers threshold on this value.","band_accuracy":"Wilson 95% interval on the measured agreement of the hand-judged records in this band.","calibrated_confidence":"WITHDRAWN. Reintroduction requires held-out evidence demonstrating reliable estimates across every bin."},"band_accuracy":{"low":{"n":210,"low":0.576,"band":"low","high":0.7046,"agree":135,"accuracy":0.6429},"high":{"n":76,"low":0.8903,"band":"high","high":0.9865,"agree":73,"accuracy":0.9605},"medium":{"n":104,"low":0.6795,"band":"medium","high":0.8397,"agree":80,"accuracy":0.7692}},"provider":"rule_based_v1+lex99e1195c7d6f","lexicon_id":"99e1195c7d6f","contract_published_at":"2026-10-23T12:25:29.022232+00:00","confidence_is_band":true,"confidence_is_probability":false,"decision_taxonomy":"two_way","decidable_fraction_two_way":0.8854,"decidable_fraction_two_way_low":0.8565,"decidable_fraction_two_way_high":0.9143,"decidable_fraction_three_way":0.8586,"decidable_fraction_three_way_low":0.8287,"decidable_fraction_three_way_high":0.8884,"decidable_population":5529,"validation_sample_size":438,"three_way_cost_fraction":0.0268,"three_way_cost_records":148,"decision_counts":{"automatable":230,"not_automatable":5299},"decision_split":{"automatable":{"count":230,"share":0.04159884246699222},"not_automatable":{"count":5299,"share":0.9584011575330078}},"diagnostic_work_type_counts":{"mixed":24,"physical":5275,"data_only":230}}}