Identification of a necroptosis-related gene signature as a novel prognostic biomarker of cholangiocarcinoma.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:36936916", "kind": "science-record", "revision": 2, "content_hash": "sha256:56564504293c97463b85249723cabfd4faf13e965a84518f71093880e45855cf", "created_at": "2026-11-01T19:01:34Z", "updated_at": "2026-11-01T21:30:23Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification of a necroptosis-related gene signature as a novel prognostic biomarker of cholangiocarcinoma.", "doi": "10.3389/fimmu.2023.1118816", "pmid": "36936916", "authors": ["Lixia Xu", "Xueping Gao", "Jiyuan Xing", "Zhixian Guo"], "journal": "Frontiers in immunology", "year": 2023, "abstract": "Background: Cholangiocarcinoma (CHOL) is the most prevalent type of malignancy and the second most common form of primary liver cancer, resulting in high rates of morbidity and mortality. Necroptosis is a type of regulated cell death that appears to be involved in the regulation of several aspects of cancer biology, including tumorigenesis, metastasis, and cancer immunity. This study aimed to construct a necroptosis-related gene (NRG) signature to investigate the prognosis of CHOL patients using an integrated bioinformatics analysis.\nMethods: CHOL patient data were acquired from the Gene Expression Omnibus (GEO) (GSE89748, GSE107943) and The Cancer Genome Atlas (TCGA) databases, with NRGs data from the necroptosis pathway in the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Univariate and multivariate regression analyses were performed to establish the NRG signatures. Kaplan-Meier (KM) curves were used to evaluate the prognosis of patients with CHOL. Functional enrichment analysis was performed to identify key NRG-associated biological signaling pathways. We also applied integrative multi-omics analysis to the high- and low-risk score groups. Spearman's rank correlation was used to clarify the relationship between the NRG signature and immune infiltration.\nResults: 65 differentially expressed (DE) NRGs were screened, five of which were selected to establish the prognostic signature of NRGS based on multivariate Cox regression analysis. We observed that low-risk patients survived significantly longer than high-risk patients. We found that patients with high-risk scores experienced higher immune cell infiltration, drug resistance, and more somatic mutations than patients with low-risk scores. We further found that sensitivities to GW843682X, mitomycin C, rapamycin, and S-trityl-L-cysteine were significantly higher in the low-risk group than in the high-risk group. Finally, we validated the expression of five NRGs in CHOL tissues using the TCGA database, HPA database and our clinical data.\nConclusion: These findings demonstrate that the five-NRG prognostic signature for CHOL patients is reasonably accurate and valid, and it may prove to be of considerable value for the treatment and prognosis of CHOL patients in the future.", "claims": [{"id": "claim-method", "statement": "The 67 DENRGs were subjected to univariate Cox proportional hazard regression analysis. Five prognostic genes (PYGB, IFNGR2, TICAM1, STAT6, and VPS4B) were selected and further analyzed using multivariate Cox proportional hazards regression analysis.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36936916", "locator": "sections[16] \"Construction of a prognostic model within necroptosis-associated genes\" paragraph 2", "quote": "The 67 DENRGs were subjected to univariate Cox proportional hazard regression analysis. Five prognostic genes (PYGB, IFNGR2, TICAM1, STAT6, and VPS4B) were selected and further analyzed using multivariate Cox proportional hazards regression analysis."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found within the article/Supplementary Material.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36936916", "locator": "sections[24] \"Data availability statement\" paragraph 2", "quote": "The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found within the article/Supplementary Material."}], "state": "complete"}, {"id": "claim-target-result", "statement": "A five-gene necroptosis-related prognostic signature was developed for CHOL, with low-risk patients surviving significantly longer than high-risk patients.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:36936916", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "65 differentially expressed (DE) NRGs were screened, five of which were selected to establish the prognostic signature of NRGS based on multivariate Cox regression analysis."}, {"asset": "source:pmid:36936916", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "We observed that low-risk patients survived significantly longer than high-risk patients."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "A five-gene necroptosis-related prognostic signature was developed for CHOL, with low-risk patients surviving significantly longer than high-risk patients.", "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:36936916"], "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:36936916", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fimmu.2023.1118816", "sha256": "sha256:c6fe587dd5dc4d981fc377706dc2028bc1d706f360002fbc8368f6c48431f791", "bytes": 44664, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fimmu.2023.1118816", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC10017743", "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 datasets presented in this study can be found in online repositories. 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RT-qPCR was performed using a thermal cycler (Roche", "ry duct tissues and 12 CHOL tissues by using RT-qPCR assay. The results showed that the expressio", "NA by using iScriptTM cDNA Synthesis Kit. RT-qPCR was performed using a thermal cycler (Roche", "duct tissues and 12 CHOL tissues by using RT-qPCR assay. The results showed that the expressio"], "order_basis": "paper_text_order:3302", "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": 0.69, "evidence": ["ptosis, NOD-like receptor signaling pathway, Apoptosis, Influenza A, TNF signaling pathway, Th17 ce"], "order_basis": "paper_text_order:4881", "id": "assay:3"}, {"role": "analysis", "definition_id": "survival_analysis", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["cox_ph"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["The 67 DENRGs were subjected to univariate Cox proportional hazard regression analysis. Five prognostic genes (PYGB, IFNGR2, TICAM1, STAT6, and VPS4B) were selected and further analyzed using multivariate Cox proportional hazards regression analysis."], "order_basis": "consumes_earlier_output", "id": "assay:4"}]}