Acyl-CoA Binding Domain Containing 4 Polymorphism rs4986172 and Expression Can Serve as Overall Survival Biomarkers for Hepatitis B Virus-Related Hepatocellular Carcinoma Patients After Hepatectomy.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:35378899", "kind": "science-record", "revision": 4, "content_hash": "sha256:6f8162bcc9f428b1c6ca46f524df86927838ed913a72af564f5ddac4e1dbf883", "created_at": "2026-11-01T18:14:11Z", "updated_at": "2026-11-01T22:48:47Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Acyl-CoA Binding Domain Containing 4 Polymorphism rs4986172 and Expression Can Serve as Overall Survival Biomarkers for Hepatitis B Virus-Related Hepatocellular Carcinoma Patients After Hepatectomy.", "doi": "10.2147/PGPM.S349350", "pmid": "35378899", "authors": ["Huasheng Huang", "Xiwen Liao", "Guangzhi Zhu", "Chuangye Han", "Xiangkun Wang", "Chengkun Yang", "Xin Zhou", "Tianyi Liang", "Ketuan Huang", "Tao Peng"], "journal": "Pharmacogenomics and personalized medicine", "year": 2022, "abstract": "Background: The aim of our study was to evaluate the potential of expression and single nucleotide polymorphism of Acyl-CoA binding domain containing 4 (ACBD4) gene as prognosis biomarkers in patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) after hepatectomy.\nMethods: HBV-related HCC patients from the First Affiliated Hospital of Guangxi Medical University and GSE14520 were included in the current study, as well as The Cancer Genome Atlas (TCGA) HCC verification cohort. Prognostic analysis and multiple functional enrichment analysis methods were used to evaluate the prognostic value and potential biological functions of the ACBD4 gene in HBV-related HCC.\nResults: We found that ACBD4 gene is highly expressed in normal liver tissues and markedly down-regulated in HBV-related HCC tissues. ACBD4 gene was significantly related to overall survival (OS) of HCC in TCGA and GSE14520 cohorts, and patients with low ACBD4 expression were markedly related to poor OS. Rs4986172 was observed as an OS biomarker after hepatectomy in the Guangxi HBV-related HCC cohort. The OS of rs4986172 GG genotype was worse than that of HCC patients with A allele (AA and AG genotypes). Multifunctional enrichment analysis suggested that ACBD4 gene is closely related to the metabolic, peroxisome proliferator-activated receptor and cytochrome P450 pathway. Through connectivity map, we also identified eight compounds that may be used as targeted therapeutic agents for ACBD4 gene in HBV-related HCC; these compounds were scopoletin, alfaxalone, bephenium hydroxynaphthoate, apramycin, 4,5-dianilinophthalimide, DL-thiorphan, aminohippuric acid and quinidine. Immune microenvironment analysis revealed that there were significant differences in immune scores of HBV-related HCC tumor tissues with different ACBD4 expression levels.\nConclusion: Our study reveals that ACBD4 expression and rs4986172 can be serve as biomarkers of OS in HBV-related HCC patients after hepatectomy.", "claims": [{"id": "claim-method", "statement": "Kaplan-Meier method and Log rank test were applied to univariate survival analysis.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35378899", "locator": "sections[4] \"Survival Analysis\" paragraph 2", "quote": "Kaplan-Meier method and Log rank test were applied to univariate survival analysis."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The authors also thank the contributors of The Cancer Genome Atlas, GSE14520, GSE25097, GSE36376, GSE54236, and GSE64041 for sharing the HCC dataset on open access.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35378899", "locator": "sections[14] \"Acknowledgments\" paragraph 2", "quote": "The authors also thank the contributors of The Cancer Genome Atlas, GSE14520, GSE25097, GSE36376, GSE54236, and GSE64041 for sharing the HCC dataset on open access."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Our study reveals that ACBD4 expression and rs4986172 can be serve as biomarkers of OS in HBV-related HCC patients after hepatectomy.", "kind": "quantitative", "target": {"value": 95.0, "unit": "per cent", "tolerance": null, "source": "Survival analysis suggested that low-ACBD4 expression in HBV-related HCC patients leads to a poor overall survival (OS) (log-rank P = 0.0016, adjusted P = 0.017, adjusted HR = 0.561, 95% CI = 0.348–0.903, Figure 2C and D, Table 1)."}, "evidence": [{"asset": "source:pmid:35378899", "locator": "sections[0] \"Abstract\" paragraph 4", "quote": "Our study reveals that ACBD4 expression and rs4986172 can be serve as biomarkers of OS in HBV-related HCC patients after hepatectomy."}, {"asset": "source:pmid:35378899", "locator": "sections[9] \"Survival Analysis\" paragraph 2", "quote": "Survival analysis suggested that low-ACBD4 expression in HBV-related HCC patients leads to a poor overall survival (OS) (log-rank P = 0.0016, adjusted P = 0.017, adjusted HR = 0.561, 95% CI = 0.348–0.903, Figure 2C and D, Table 1)."}, {"asset": "source:pmid:35378899", "locator": "sections[9] \"Survival Analysis\" paragraph 11", "quote": "Subsequently, we combined patients with A allele (AA+AG) and found that HBV-related HCC patients with A allele had a better OS than those with GG genotype (log-rank P = 0.0015, adjusted P = 0.012, HR = 0.666, 95% CI = 0.486–0.913, Figure 7B, Table 3)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Our study reveals that ACBD4 expression and rs4986172 can be serve as biomarkers of OS in HBV-related HCC patients after hepatectomy.", "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:35378899"], "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:GSE14520"], "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:GSE14520"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:35378899", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.2147/PGPM.S349350", "sha256": "sha256:5e0daa735d7d50dd11a7df46d51ed2cd0ca1e2764bd2e1a8306a0527ae7891c7", "bytes": 50623, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.2147/PGPM.S349350", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC8976523", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE14520", "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=GSE14520", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE14520", "version": null, "note": "The authors also thank the contributors of The Cancer Genome Atlas, GSE14520, GSE25097, GSE36376, GSE54236, and GSE64041 for sharing the HCC dataset on open access.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The authors also thank the contributors of The Cancer Genome Atlas, GSE14520, GSE25097, GSE36376, GSE54236, and GSE64041 for sharing the HCC dataset on open access.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM362947", "GSM362948", "GSM362949", "GSM362950", "GSM362951", "GSM362952", "GSM362953", "GSM362954", "GSM362955", "GSM362956", "GSM362957", "GSM362958", "GSM362959", "GSM362960", "GSM362961", "GSM362962", "GSM362963", "GSM362964", "GSM362965", "GSM362966", "GSM362967", "GSM362968", "GSM362969", "GSM362970", "GSM362971", "GSM362972", "GSM362973", "GSM362974", "GSM362975", "GSM362976", "GSM362977", "GSM362978", "GSM362979", "GSM362980", "GSM362981", "GSM362982", "GSM362983", "GSM362984", "GSM362985", "GSM362986", "GSM362987", "GSM362988", "GSM362989", "GSM362990", "GSM362991", "GSM362992", "GSM362993", "GSM362994", "GSM362995", "GSM362996", "GSM362997", "GSM362998", "GSM362999", "GSM363000", "GSM363001", "GSM363002", "GSM363003", "GSM363004", "GSM363005", "GSM363006", "GSM363007", "GSM363008", "GSM363009", "GSM363010", "GSM363011", "GSM363012", "GSM363013", "GSM363014", "GSM363015", "GSM363016", "GSM363017", "GSM363018", "GSM363019", "GSM363020", "GSM363021", "GSM363022", "GSM363023", "GSM363024", "GSM363025", "GSM363026", "GSM363027", "GSM363028", "GSM363029", "GSM363030", "GSM363031", "GSM363032", "GSM363033", "GSM363034", "GSM363035", "GSM363036", "GSM363037", "GSM363038", "GSM363039", "GSM363040", "GSM363041", "GSM363042", "GSM363043", "GSM363044", "GSM363045", "GSM363046", "GSM363047", "GSM363048", "GSM363049", "GSM363050", "GSM363051", "GSM363052", "GSM363053", "GSM363054", "GSM363055", "GSM363056", "GSM363057", "GSM363058", "GSM363059", "GSM363060", "GSM363061", "GSM363062", "GSM363063", "GSM363064", "GSM363065", "GSM363066", "GSM363067", "GSM363068", "GSM363069", "GSM363070", "GSM363071", "GSM363072", "GSM363073", "GSM363074", "GSM363075", "GSM363076", "GSM363077", "GSM363078", "GSM363079", "GSM363080", "GSM363081", "GSM363082", "GSM363083", "GSM363084", "GSM363085", "GSM363086", "GSM363087", "GSM363088", "GSM363089", "GSM363090", "GSM363091", "GSM363092", "GSM363093", "GSM363094", "GSM363095", "GSM363096", "GSM363097", "GSM363098", "GSM363099", "GSM363100", "GSM363101", "GSM363102", "GSM363103", "GSM363104", "GSM363105", "GSM363106", "GSM363107", "GSM363108", "GSM363109", "GSM363110", "GSM363111", "GSM363112", "GSM363113", "GSM363114", "GSM363115", "GSM363116", "GSM363117", "GSM363118", "GSM363119", "GSM363120", "GSM363121", "GSM363122", "GSM363123", "GSM363124", "GSM363125", "GSM363126", "GSM363127", "GSM363128", "GSM363129", "GSM363130", "GSM363131", "GSM363132", "GSM363133", "GSM363134", "GSM363135", "GSM363136", "GSM363137", "GSM363138", "GSM363139", "GSM363140", "GSM363141", "GSM363142", "GSM363143", "GSM363144", "GSM363145", "GSM363146", "GSM363147", "GSM363148", "GSM363149", "GSM363150", "GSM363151", "GSM363152", "GSM363153", "GSM363154", "GSM363155", "GSM363156", "GSM363157", "GSM363158", "GSM363159", "GSM363160", "GSM363161", "GSM363162", "GSM363163", "GSM363164", "GSM363165", "GSM363166", "GSM363167", "GSM363168", "GSM363169", "GSM363170", "GSM363171", "GSM363172", "GSM363173", "GSM363174", "GSM363175", "GSM363176", "GSM363177", "GSM363178", "GSM363179", "GSM363180", "GSM363181", "GSM363182", "GSM363183", "GSM363184", "GSM363185", "GSM363186", "GSM363187", "GSM363188", "GSM363189", "GSM363190", "GSM363191", "GSM363192", "GSM363193", "GSM363194", "GSM363195", "GSM363196", "GSM363197", "GSM363198", "GSM363199", "GSM363200", "GSM363201", "GSM363202", "GSM363203", "GSM363204", "GSM363205", "GSM363206", "GSM363207", "GSM363208", "GSM363209", "GSM363210", "GSM363211", "GSM363212", "GSM363213", "GSM363214", "GSM363215", "GSM363216", "GSM363217", "GSM363218", "GSM363219", "GSM363220", "GSM363221", "GSM363222", "GSM363223", "GSM363224", "GSM363225", "GSM363226", "GSM363227", "GSM363228", "GSM363229", "GSM363230", "GSM363231", "GSM363232", "GSM363233", "GSM363234", "GSM363235", "GSM363236", "GSM363237", "GSM363238", "GSM363239", "GSM363240", "GSM363241", "GSM363242", "GSM363243", "GSM363244", "GSM363245", "GSM363246", "GSM363247", "GSM363248", "GSM363249", "GSM363250", "GSM363251", "GSM363252", "GSM363253", "GSM363254", "GSM363255", "GSM363256", "GSM363257", "GSM363258", "GSM363259", "GSM363260", "GSM363261", "GSM363262", "GSM363263", "GSM363264", "GSM363265", "GSM363266", "GSM363267", "GSM363268", "GSM363269", "GSM363270", "GSM363271", "GSM363272", "GSM363273", "GSM363274", "GSM363275", "GSM363276", "GSM363277", "GSM363278", "GSM363279", "GSM363280", "GSM363281", "GSM363282", "GSM363283", "GSM363284", "GSM363285", "GSM363286", "GSM363287", "GSM363288", "GSM363289", "GSM363290", "GSM363291", "GSM363292", "GSM363293", "GSM363294", "GSM363295", "GSM363296", "GSM363297", "GSM363298", "GSM363299", "GSM363300", "GSM363301", "GSM363302", "GSM363303", "GSM363304", "GSM363305", "GSM363306", "GSM363307", "GSM363308", "GSM363309", "GSM363310", "GSM363311", "GSM363312", "GSM363313", "GSM363314", "GSM363315", "GSM363316", "GSM363317", "GSM363318", "GSM363319", "GSM363320", "GSM363321", "GSM363322", "GSM363323", "GSM363324", "GSM363325", "GSM363326", "GSM363327", "GSM363328", "GSM363329", "GSM363330", "GSM363331", "GSM363332", "GSM363333", "GSM363334", "GSM363335", "GSM363336", "GSM363337", "GSM363338", "GSM363339", "GSM363340", "GSM363341", "GSM363342", "GSM363343", "GSM363344", "GSM363345", "GSM363346", "GSM363347", "GSM363348", "GSM363349", "GSM363350", "GSM363351", "GSM363352", "GSM363353", "GSM363354", "GSM363355", "GSM363356", "GSM363357", "GSM363358", "GSM363359", "GSM363360", "GSM363361", "GSM363362", "GSM363363", "GSM363364", "GSM363365", "GSM363366", "GSM363367", "GSM363368", "GSM363369", "GSM363370", "GSM363371", "GSM363372", "GSM363373", "GSM363374", "GSM363375", "GSM363376", "GSM363378", "GSM363380", "GSM363381", "GSM363382", "GSM363384", "GSM363386", "GSM363388", "GSM363391", "GSM363393", "GSM363397", "GSM363400", "GSM363402", "GSM363404", "GSM363407", "GSM363417", "GSM363420", "GSM363421", "GSM363422", "GSM363423", "GSM363424", "GSM363425", "GSM363426", "GSM363427", "GSM363428", "GSM363429", "GSM363430", "GSM363431", "GSM363432", "GSM363433", "GSM363434", "GSM363435", "GSM363436", "GSM363437", "GSM363438", "GSM363439", "GSM363440", "GSM363441", "GSM363442", "GSM363443", "GSM363444", "GSM363445", "GSM363446", "GSM363447", "GSM363448", "GSM363449", "GSM363450", "GSM363451", "GSM712532", "GSM712533", "GSM712534", "GSM712535", "GSM712536", "GSM712537", "GSM712538", "GSM712539", "GSM712540", "GSM712541", "GSM712542"], "sample_count": 488, "group_sizes": null, "group_sizes_basis": null, "platform": "3921;571", "taxon": "Homo sapiens", "title": "Gene expression data of human hepatocellular carcinoma (HCC)", "resolution_checked_at": "2026-11-01T15:39:54Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}], "gaps": ["asset:data:geo:GSE14520 not downloaded", "asset:data:geo:GSE14520 licence not read"]}, "analysis": {"state": "complete", "methods": [{"id": "method-1", "family": "survival_analysis", "specific": "kaplan_meier", "label": "Survival analysis", "dsl_operations": ["survival_km"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["time_to_event_with_censoring"], "evidence": {"score": 1.0, "band": "verbatim", "quote": "Kaplan-Meier method and Log rank test were applied to univariate survival analysis."}}, {"id": "method-2", "family": "survival_analysis", "specific": "log_rank_test", "label": "Survival analysis", "dsl_operations": ["logrank_test"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["time_to_event_with_censoring"], "evidence": {"score": 0.8, "band": "high", "quote": "Log rank"}}, {"id": "method-3", "family": "regression_modelling", "specific": "logistic", "label": "Regression modelling", "dsl_operations": ["glm_logit_fit"], "missing_operations": [], "expressible": true, "parameters": {"coefficient": "linical parameters, and odds ratio (OR) was used to evalua"}, "data_shapes": ["predictors_and_outcome"], "evidence": {"score": 0.8, "band": "high", "quote": "logistic regression"}}], "targets": [{"id": "target-published-estimate", "claim_id": "claim-target-result", "operation": "glm_logit_fit", "expected_value": 95.0, "unit": "per cent", "tolerance": null, "state": "complete", "note": "The published estimate as the reader quoted it from the paper. No tolerance is published because the paper states none."}], "gaps": []}, "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": ["survival_km"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: kaplan_meier."}, "capability": {"tier": "R1", "capability_id": "capability:computational_analysis", "availability_state": "owned", "basis": "The computational analysis is owned. The physical bench the paper used is not, so a physical validation cannot be run here."}, "data": {"tier": "R1", "reachable": true, "accessions": ["GSE14520"], "resolved_accessions": ["GSE14520"], "statements": ["The authors also thank the contributors of The Cancer Genome Atlas, GSE14520, GSE25097, GSE36376, GSE54236, and GSE64041 for sharing the HCC dataset on open access."], "basis": "The paper names GSE14520 in Gene Expression Omnibus and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["survival_km"], "assets": ["source:pmid:35378899", "data:geo:GSE14520"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE14520"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T17:40:52Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 14310, "completion_tokens": 3145, "cached_tokens": 256}}, "human_critique": null, "stages": [{"id": "extraction", "state": "complete", "reader": "MiniMax-M3.1-Flash", "provider": "minimax"}], "gaps": ["review.independent_reader", "review.machine_critique", "review.human_critique"]}, "execution": {"state": "absent", "status": "not_run", "mode": null, "runs": [], "gaps": ["execution.not_run"]}, "provenance": {"entities": [{"id": "pmid:35378899", "type": "paper", "label": "pmid:35378899"}, {"id": "source:pmid:35378899", "type": "manuscript", "label": "PMID 35378899 full text"}, {"id": "data:geo:GSE14520", "type": "dataset", "label": "GEO GSE14520"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:35378899", "type": "paper", "label": "pmid:35378899"}, {"id": "source:pmid:35378899", "type": "manuscript", "label": "PMID 35378899 full text"}, {"id": "data:geo:GSE14520", "type": "dataset", "label": "GEO GSE14520"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-35378899", "type": "extraction", "used": ["source:pmid:35378899"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE14520", "type": "accession_resolution", "used": ["data:geo:GSE14520"], "agent": "agent:corpus-assay-engine"}], "agents": [{"id": "agent:corpus-assay-engine", "type": "software", "label": "Corpus assay engine"}, {"id": "agent:minimax-reader", "type": "software", "label": "MiniMax literature reader"}], "source_run_id": "reading-sci-2026-11-01", "dsl_catalogue_fingerprint": "343fb30756ba6ec3", "capability_table_fingerprint": "2cb3e42f047d2ecf", "snapshot_id": "ba34b49490d9bfaf"}, "lineage": {"parent_id": "pmid:35378899", "parent_hash": "sha256:9d55d7cbd552426d464e58918537075d6ccfc6d7eeb46f4105bf8b816cb79d2a", "fork_of": null, "generation": 3}, "gaps": ["asset:data:geo:GSE14520 licence not read", "asset:data:geo:GSE14520 not downloaded", "execution.not_run", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "analysis", "definition_id": "survival_analysis", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["survival_km"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["Kaplan-Meier method and Log rank test were applied to univariate survival analysis."], "order_basis": "analysis_only", "id": "assay:1"}]}