ACSL4 serves as a novel prognostic biomarker correlated with immune infiltration in Cholangiocarcinoma.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:37193981", "kind": "science-record", "revision": 3, "content_hash": "sha256:b0f4719c787d71f60eb4a975d30bc1d4558b4216d35acdb4be66f92ba8d7ceab", "created_at": "2026-11-01T19:01:53Z", "updated_at": "2026-11-01T22:09:29Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "ACSL4 serves as a novel prognostic biomarker correlated with immune infiltration in Cholangiocarcinoma.", "doi": "10.1186/s12885-023-10903-5", "pmid": "37193981", "authors": ["Shuochen Liu", "Shilong Fan", "Yirui Wang", "Ruixiang Chen", "Ziyi Wang", "Yaodong Zhang", "Wangjie Jiang", "Yananlan Chen", "Xiao Xu", "Yue Yu", "Changxian Li", "Xiangcheng Li"], "journal": "BMC cancer", "year": 2023, "abstract": "BACKGROUND: Cholangiocarcinoma (CHOL) is the second most common primary hepatic malignant tumor, following hepatocellular carcinoma (HCC). CHOL is highly aggressive and heterogeneous resulting in poor prognosis. The diagnosis and prognosis of CHOL has not improved in the past decade. Acyl-CoA synthetase long-chain family member 4 (ACSL4) is reported to be associated with tumors, however, its role in CHOL has not been revealed. This study is mainly for exploring the prognostic values and potential function of ACSL4 in CHOL.\nMETHODS: We investigated the expression level and prognostic value of ACSL4 in CHOL based on The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets. TIMER2.0, TISIDB and CIBERSORT databases were utilized to assess the associations between ACSL4 and immune infiltration cells in CHOL. Single-cell sequencing data from GSE138709 was analyzed to study the expression of ACSL4 in different types of cells. ACSL4 co-expressed genes were analyzed by Linkedomics. Additionally, Western Blot, qPCR, EdU assay, CCK8 assay, transwell assay and wound healing assay were performed to further confirm the roles of ACSL4 in the pathogenesis of CHOL.\nRESULTS: We found that the level of ACSL4 was higher in CHOL and it was correlated with the diagnosis and prognosis of CHOL patients. Then, we observed that the infiltration level of immune cells was related to the level of ACSL4 in CHOL. Moreover, ACSL4 and its co-expressed genes were mainly enriched in metabolism-related pathway and ACSL4 is also a key pro-ferroptosis gene in CHOL. Finally, knockdown of ACSL4 could reverse the tumor-promoting effect of ACSL4 in CHOL.\nCONCLUSIONS: The current findings demonstrated ACSL4 may as a novel biomarker for CHOL patients, which might regulate immune microenvironment and metabolism resulting in poor prognosis.", "claims": [{"id": "claim-method", "statement": "Associations were evaluated using Spearman’s correlation analysis.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37193981", "locator": "sections[14] \"Statistical analysis\" paragraph 2", "quote": "Associations were evaluated using Spearman’s correlation analysis."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The original contributions presented during this study are included in this published article. The datasets analyzed during the current study are available in the GEO repository (https://www.ncbi.nlm.nih.gov/geo, GEO accession number: GSE76297, GSE107943 and GSE138709), TCGA repository (https://www.cancer.gov/tcga), TIMER2.0 repository (http://timer.cistrome.org/), HPA repository (http://www.proteinatlas.org/), TISIDB repository (http://cis.hku.hk/TISIDB/), LinkedOmics repository (http://www.linkedomics.org/login.php).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37193981", "locator": "sections[30] \"notes\" paragraph 1", "quote": "The original contributions presented during this study are included in this published article. The datasets analyzed during the current study are available in the GEO repository (https://www.ncbi.nlm.nih.gov/geo, GEO accession number: GSE76297, GSE107943 and GSE138709), TCGA repository (https://www.cancer.gov/tcga), TIMER2.0 repository (http://timer.cistrome.org/), HPA repository (http://www.proteinatlas.org/), TISIDB repository (http://cis.hku.hk/TISIDB/), LinkedOmics repository (http://www.linkedomics.org/login.php)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "", "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:37193981"], "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:GSE107943"], "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:GSE107943"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:37193981", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1186/s12885-023-10903-5", "sha256": "sha256:8aef8a23ff4b4b58cbb2d4a9f26ac4c2b14f45d8e1845fa7bbb81d85cdff4783", "bytes": 34673, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1186/s12885-023-10903-5", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC10186676", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE107943", "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=GSE107943", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE107943", "version": null, "note": "The original contributions presented during this study are included in this published article. The datasets analyzed during the current study are available in the GEO repository (https://www.ncbi.nlm.nih.gov/geo, GEO accession number: GSE76297, GSE107943 and GSE138709), TCGA repository (https://www.cancer.gov/tcga), TIMER2.0 repository (http://timer.cistrome.org/), HPA repository (http://www.proteinatlas.org/), TISIDB repository (http://cis.hku.hk/TISIDB/), LinkedOmics repository (http://www.linkedomics.org/login.php).", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The original contributions presented during this study are included in this published article. The datasets analyzed during the current study are available in the GEO repository (https://www.ncbi.nlm.nih.gov/geo, GEO accession number: GSE76297, GSE107943 and GSE138709), TCGA repository (https://www.cancer.gov/tcga), TIMER2.0 repository (http://timer.cistrome.org/), HPA repository (http://www.proteinatlas.org/), TISIDB repository (http://cis.hku.hk/TISIDB/), LinkedOmics repository (http://www.linkedomics.org/login.php).", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM2883928", "GSM2883929", "GSM2883930", "GSM2883931", "GSM2883932", "GSM2883933", "GSM2883934", "GSM2883935", "GSM2883936", "GSM2883937", "GSM2883938", "GSM2883939", "GSM2883940", "GSM2883941", "GSM2883942", "GSM2883943", "GSM2883944", "GSM2883945", "GSM2883946", "GSM2883947", "GSM2883948", "GSM2883949", "GSM2883950", "GSM2883951", "GSM2883952", "GSM2883953", "GSM2883954", "GSM2883955", "GSM2883956", "GSM2883957", "GSM2883958", "GSM2883959", "GSM2883960", "GSM2883961", "GSM2883962", "GSM2883963", "GSM2883964", "GSM2883965", "GSM2883966", "GSM2883967", "GSM2883968", "GSM2883969", "GSM2883970", "GSM2883971", "GSM2883972", "GSM2883973", "GSM2883974", "GSM2883975", "GSM2883976", "GSM2883977", "GSM2883978", "GSM2883979", "GSM2883980", "GSM2883981", "GSM2883982", "GSM2883983", "GSM2883984"], "sample_count": 57, "group_sizes": null, "group_sizes_basis": null, "platform": "18573", "taxon": "Homo sapiens", "title": "Integrative molecular and clinical analysis of intrahepatic cholangiocarcinoma reveals two prognostic subclassees", "resolution_checked_at": "2026-11-01T17:30:42Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE138709", "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=GSE138709", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE138709", "version": null, "note": "The original contributions presented during this study are included in this published article. The datasets analyzed during the current study are available in the GEO repository (https://www.ncbi.nlm.nih.gov/geo, GEO accession number: GSE76297, GSE107943 and GSE138709), TCGA repository (https://www.cancer.gov/tcga), TIMER2.0 repository (http://timer.cistrome.org/), HPA repository (http://www.proteinatlas.org/), TISIDB repository (http://cis.hku.hk/TISIDB/), LinkedOmics repository (http://www.linkedomics.org/login.php).", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The original contributions presented during this study are included in this published article. The datasets analyzed during the current study are available in the GEO repository (https://www.ncbi.nlm.nih.gov/geo, GEO accession number: GSE76297, GSE107943 and GSE138709), TCGA repository (https://www.cancer.gov/tcga), TIMER2.0 repository (http://timer.cistrome.org/), HPA repository (http://www.proteinatlas.org/), TISIDB repository (http://cis.hku.hk/TISIDB/), LinkedOmics repository (http://www.linkedomics.org/login.php).", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM4116579", "GSM4116580", "GSM4116581", "GSM4116582", "GSM4116583", "GSM4116584", "GSM4116585", "GSM4116586"], "sample_count": 8, "group_sizes": null, "group_sizes_basis": null, "platform": "24676;20795", "taxon": "Homo sapiens", "title": "Dissecting the transcriptomic landscape of the human intrahepatic cholangiocarcinoma by single cell RNA-sequencing", "resolution_checked_at": "2026-11-01T15:39:54Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE76297", "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=GSE76297", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE76297", "version": null, "note": "The original contributions presented during this study are included in this published article. 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The datasets analyzed during the current study are available in the GEO repository (https://www.ncbi.nlm.nih.gov/geo, GEO accession number: GSE76297, GSE107943 and GSE138709), TCGA repository (https://www.cancer.gov/tcga), TIMER2.0 repository (http://timer.cistrome.org/), HPA repository (http://www.proteinatlas.org/), TISIDB repository (http://cis.hku.hk/TISIDB/), LinkedOmics repository (http://www.linkedomics.org/login.php).", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM1979367", "GSM1979368", "GSM1979369", "GSM1979370", "GSM1979371", "GSM1979372", "GSM1979373", "GSM1979374", "GSM1979375", "GSM1979376", "GSM1979377", "GSM1979378", "GSM1979379", "GSM1979380", "GSM1979381", "GSM1979382", "GSM1979383", "GSM1979384", "GSM1979385", "GSM1979386", "GSM1979387", "GSM1979388", "GSM1979389", "GSM1979390", "GSM1979391", "GSM1979392", "GSM1979393", "GSM1979394", "GSM1979395", "GSM1979396", "GSM1979397", "GSM1979398", "GSM1979399", "GSM1979400", "GSM1979401", 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The physical bench the paper used is not, so a physical validation cannot be run here."}, "data": {"tier": "R1", "reachable": true, "accessions": ["GSE76297", "GSE107943", "GSE138709"], "resolved_accessions": ["GSE76297", "GSE107943", "GSE138709"], "statements": ["The original contributions presented during this study are included in this published article. The datasets analyzed during the current study are available in the GEO repository (https://www.ncbi.nlm.nih.gov/geo, GEO accession number: GSE76297, GSE107943 and GSE138709), TCGA repository (https://www.cancer.gov/tcga), TIMER2.0 repository (http://timer.cistrome.org/), HPA repository (http://www.proteinatlas.org/), TISIDB repository (http://cis.hku.hk/TISIDB/), LinkedOmics repository (http://www.linkedomics.org/login.php)."], "basis": "The paper names GSE76297, GSE107943, GSE138709 in Gene Expression Omnibus (GEO) and the accession resolves in the repository. 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Additionally, Western Blot, qPCR, EdU assay, CCK8 assay, transwell assa"], "order_basis": "paper_text_order:1079", "id": "assay:1"}, {"role": "data_generation", "definition_id": "qpcr", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["by Linkedomics. Additionally, Western Blot, qPCR, EdU assay, CCK8 assay, transwell assay and"], "order_basis": "paper_text_order:1093", "id": "assay:2"}, {"role": "data_generation", "definition_id": "apoptosis_assay", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["Additionally, Western Blot, qPCR, EdU assay, CCK8 assay, transwell assay and wound healing ass"], "order_basis": "paper_text_order:1109", "id": "assay:3"}, {"role": "data_generation", "definition_id": "transfection", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["a key pro-ferroptosis gene in CHOL. Finally, knockdown of ACSL4 could reverse the tumor-promoting e", "ng to regional regulations. Cell culture and transfection Human intrahepatic biliary epithelial cell l", "0 (11,668,019, Invitrogen, USA) was used for transfection following the manufacturer’s protocol. The f", "g the manufacturer’s protocol. The following siRNA sequences were used: ACSL4 sense 5′-GAGGCUUC"], "order_basis": "paper_text_order:1639", "id": "assay:4"}, {"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": ["9 were used in our study. All the cells were cultured in DMEM High Glucose (Biochannel, China) contai"], "order_basis": "paper_text_order:2535", "id": "assay:5"}, {"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": 0.8, "evidence": ["Kaplan-Meier"], "order_basis": "consumes_earlier_output", "id": "assay:6"}]}