A new nomogram model for prognosis of hepatocellular carcinoma based on novel gene signature that regulates cross-talk between immune and tumor cells.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:35397536", "kind": "science-record", "revision": 4, "content_hash": "sha256:9f146ab573580e964487839e5d577d895fd8c01666129428564243bbdd437c26", "created_at": "2026-11-01T18:14:12Z", "updated_at": "2026-11-01T22:06:16Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "A new nomogram model for prognosis of hepatocellular carcinoma based on novel gene signature that regulates cross-talk between immune and tumor cells.", "doi": "10.1186/s12885-022-09465-9", "pmid": "35397536", "authors": ["Youpeng Wang", "Yeni Yang", "Ziyin Zhao", "Hongfa Sun", "Dingan Luo", "Lakshmi Huttad", "Bingyuan Zhang", "Bing Han"], "journal": "BMC cancer", "year": 2022, "abstract": "BACKGROUND: The combined application of immune cells and specific biomarkers related to the tumor immune microenvironment has a better predictive value for the prognosis of HCC. The purpose of this study is to construct a new prognostic model based on immune-related genes that regulate cross-talk between immune and tumor cells to assess the prognosis and explore possible mechanisms.\nMETHOD: The immune cell abundance ratio of 424 cases in the TCGA-LIHC database is obtained through the CIBERSORT algorithm. The differential gene analysis and cox regression analysis is used to screen IRGs. In addition, the function of IRGs was preliminarily explored through the co-culture of M2 macrophages and HCC cell lines. The clinical validation, nomogram establishment and performing tumor microenvironment score were validated.\nRESULTS: We identified 4 immune cells and 9 hub genes related to the prognosis. Further, we identified S100A9, CD79B, TNFRSF11B as an IRGs signature, which is verified in the ICGC and GSE76427 database. Importantly, IRGs signature is closely related to the prognosis, tumor microenvironment score, clinical characteristics and immunotherapy, and nomogram combined with clinical characteristics is more conducive to clinical promotion. In addition, after co-culture with M2 macrophages, the migration capacity and cell pseudopod of MHCC97H increased significantly. And CD79B and TNFRSF11B were significantly down-regulated in MHCC97H, Huh7 and LM3, while S100A9 was up-regulated.\nCONCLUSION: We constructed an IRGs signature and discussed possible mechanisms. The nomogram established based on IRGs can accurately predict the prognosis of HCC patients. These findings may provide a suitable therapeutic target for HCC.", "claims": [{"id": "claim-method", "statement": "The RNA-Seq (FPKM format) of 424 specimens were analyzed using the CIBERSORT algorithm and obtained a ratio matrix of 22 immune cells (perm = 100) [14, 15].", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35397536", "locator": "sections[4] \"Identifying survival-related immune cells\" paragraph 2", "quote": "The RNA-Seq (FPKM format) of 424 specimens were analyzed using the CIBERSORT algorithm and obtained a ratio matrix of 22 immune cells (perm = 100) [14, 15]."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets analysed during the current study are available in TCGA, ICGC and GSE76427. (http://portal.gdc.cancer.gov/, https://dcc.icgc.org/, https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE76427) All data and outcomes generated during this study are included in this published article and its supplementary information files.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35397536", "locator": "sections[37] \"Availability of data and materials\" paragraph 2", "quote": "The datasets analysed during the current study are available in TCGA, ICGC and GSE76427. (http://portal.gdc.cancer.gov/, https://dcc.icgc.org/, https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE76427) All data and outcomes generated during this study are included in this published article and its supplementary information files."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The study identified four survival-related immune cells, nine prognostic hub genes, and a three-gene IRGs signature, and constructed a nomogram for predicting survival in HCC patients.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:35397536", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "We identified 4 immune cells and 9 hub genes related to the prognosis."}, {"asset": "source:pmid:35397536", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "Further, we identified S100A9, CD79B, TNFRSF11B as an IRGs signature, which is verified in the ICGC and GSE76427 database."}, {"asset": "source:pmid:35397536", "locator": "sections[0] \"Abstract\" paragraph 4", "quote": "We constructed an IRGs signature and discussed possible mechanisms."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The study identified four survival-related immune cells, nine prognostic hub genes, and a three-gene IRGs signature, and constructed a nomogram for predicting survival in HCC 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:35397536"], "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:GSE76427"], "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:GSE76427"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:35397536", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1186/s12885-022-09465-9", "sha256": "sha256:c478b4e2e75276a5268fcee050351eb6aa73c4271bcfa307e64c1d78c7eb2aef", "bytes": 59377, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1186/s12885-022-09465-9", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC8994280", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE76427", "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=GSE76427", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE76427", "version": null, "note": "The datasets analysed during the current study are available in TCGA, ICGC and GSE76427. (http://portal.gdc.cancer.gov/, https://dcc.icgc.org/, https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE76427) All data and outcomes generated during this study are included in this published article and its supplementary information files.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The datasets analysed during the current study are available in TCGA, ICGC and GSE76427. (http://portal.gdc.cancer.gov/, https://dcc.icgc.org/, https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE76427) All data and outcomes generated during this study are included in this published article and its supplementary information files.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM2011285", "GSM2011286", "GSM2011287", "GSM2011288", "GSM2011289", "GSM2011290", "GSM2011291", "GSM2011292", "GSM2011293", "GSM2011294", "GSM2011295", "GSM2011296", "GSM2011297", "GSM2011298", "GSM2011299", "GSM2011300", "GSM2011301", "GSM2011302", "GSM2011303", "GSM2011304", "GSM2011305", "GSM2011306", "GSM2011307", "GSM2011308", "GSM2011309", "GSM2011310", "GSM2011311", "GSM2011312", "GSM2011313", "GSM2011314", "GSM2011315", "GSM2011316", "GSM2011317", "GSM2011318", "GSM2011319", "GSM2011320", "GSM2011321", "GSM2011322", "GSM2011323", "GSM2011324", "GSM2011325", "GSM2011326", "GSM2011327", "GSM2011328", "GSM2011329", "GSM2011330", "GSM2011331", "GSM2011332", "GSM2011333", "GSM2011334", "GSM2011335", "GSM2011336", "GSM2011337", "GSM2011338", "GSM2011339", "GSM2011340", "GSM2011341", "GSM2011342", "GSM2011343", "GSM2011344", "GSM2011345", "GSM2011346", "GSM2011347", "GSM2011348", "GSM2011349", "GSM2011350", "GSM2011351", "GSM2011352", "GSM2011353", "GSM2011354", "GSM2011355", "GSM2011356", "GSM2011357", "GSM2011358", "GSM2011359", "GSM2011360", "GSM2011361", "GSM2011362", "GSM2011363", "GSM2011364", "GSM2011365", "GSM2011366", "GSM2011367", "GSM2011368", "GSM2011369", "GSM2011370", "GSM2011371", "GSM2011372", "GSM2011373", "GSM2011374", "GSM2011375", "GSM2011376", "GSM2011377", "GSM2011378", "GSM2011379", "GSM2011380", "GSM2011381", "GSM2011382", "GSM2011383", "GSM2011384", "GSM2011385", "GSM2011386", "GSM2011387", "GSM2011388", "GSM2011389", "GSM2011390", "GSM2011391", "GSM2011392", "GSM2011393", "GSM2011394", "GSM2011395", "GSM2011396", "GSM2011397", "GSM2011398", "GSM2011399", "GSM2011400", "GSM2011401", "GSM2011402", "GSM2011403", "GSM2011404", "GSM2011405", "GSM2011406", "GSM2011407", "GSM2011408", "GSM2011409", "GSM2011410", "GSM2011411", "GSM2011412", "GSM2011413", "GSM2011414", "GSM2011415", "GSM2011416", "GSM2011417", "GSM2011418", "GSM2011419", "GSM2011420", "GSM2011421", "GSM2011422", "GSM2011423", "GSM2011424", "GSM2011425", "GSM2011426", "GSM2011427", "GSM2011428", "GSM2011429", "GSM2011430", "GSM2011431", "GSM2011432", "GSM2011433", "GSM2011434", "GSM2011435", "GSM2011436", "GSM2011437", "GSM2011438", "GSM2011439", "GSM2011440", "GSM2011441", "GSM2011442", "GSM2011443", "GSM2011444", "GSM2011445", "GSM2011446", "GSM2011447", "GSM2011448", "GSM2011449", "GSM2011450", "GSM2011451"], "sample_count": 167, "group_sizes": null, "group_sizes_basis": null, "platform": "10558", "taxon": "Homo sapiens", "title": "Microarray expression data for tumor and adjacent non-tumor tissues from hepatocellular carcinoma patients", "resolution_checked_at": "2026-11-01T15:39:55Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}], "gaps": ["asset:data:geo:GSE76427 not downloaded", "asset:data:geo:GSE76427 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "family": "survival_analysis", "specific": "cox_proportional_hazards", "label": "Survival analysis", "dsl_operations": ["cox_ph"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["time_to_event_with_censoring"], "evidence": {"score": 0.7, "band": "medium", "quote": "cox regression"}}, {"id": "method-2", "family": "differential_expression", "specific": "edger", "label": "Differential expression analysis", "dsl_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "missing_operations": [], "expressible": true, "parameters": {"log2fc_threshold": "A with the conditions: |logFC|> 1 and P < 0"}, "data_shapes": ["count_matrix_with_condition"], "evidence": {"score": 0.8, "band": "high", "quote": "edgeR"}}, {"id": "method-3", "family": null, "specific": null, "label": "CIBERSORT algorithm", "dsl_operations": [], "missing_operations": [], "expressible": null, "parameters": {}, "data_shapes": [], "evidence": {"score": 1.0, "band": "verbatim", "quote": "The RNA-Seq (FPKM format) of 424 specimens were analyzed using the CIBERSORT algorithm and obtained a ratio matrix of 22 immune cells (perm = 100) [14, 15]."}}], "targets": [], "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": ["cox_ph"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: cox_proportional_hazards."}, "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": ["GSE76427"], "resolved_accessions": ["GSE76427"], "statements": ["The datasets analysed during the current study are available in TCGA, ICGC and GSE76427. (http://portal.gdc.cancer.gov/, https://dcc.icgc.org/, https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE76427) All data and outcomes generated during this study are included in this published article and its supplementary information files."], "basis": "The paper names GSE76427 in GEO and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["cox_ph"], "assets": ["source:pmid:35397536", "data:geo:GSE76427"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE76427"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T17:41:07Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 17184, "completion_tokens": 2109, "cached_tokens": 128}}, "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:35397536", "type": "paper", "label": "pmid:35397536"}, {"id": "source:pmid:35397536", "type": "manuscript", "label": "PMID 35397536 full text"}, {"id": "data:geo:GSE76427", "type": "dataset", "label": "GEO GSE76427"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:35397536", "type": "paper", "label": "pmid:35397536"}, {"id": "source:pmid:35397536", "type": "manuscript", "label": "PMID 35397536 full text"}, {"id": "data:geo:GSE76427", "type": "dataset", "label": "GEO GSE76427"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-35397536", "type": "extraction", "used": ["source:pmid:35397536"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE76427", "type": "accession_resolution", "used": ["data:geo:GSE76427"], "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:35397536", "parent_hash": "sha256:e5e80a1bc9c00b73fef8421c1c6804b979bf69a136d68c2a85ae2f69bdf4f675", "fork_of": null, "generation": 3}, "gaps": ["asset:data:geo:GSE76427 licence not read", "asset:data:geo:GSE76427 not downloaded", "execution.not_run", "method.reader_named_unmapped", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "data_generation", "definition_id": "rna_seq", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["\"ESTIMATE\" to study the expression level of RNA-seq to count the tumor purity, estimate score(ES"], "order_basis": "paper_text_order:2913", "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": ["n. Additional file 2: Supplementary Table 1. qPCR primer sequence. Additional file 3: Suppleme"], "order_basis": "paper_text_order:6455", "id": "assay:2"}, {"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": 0.7, "evidence": ["cox regression"], "order_basis": "consumes_earlier_output", "id": "assay:3"}]}