Identification of an immune-related gene signature as a prognostic target and the immune microenvironment for adrenocortical carcinoma.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:36039643", "kind": "science-record", "revision": 4, "content_hash": "sha256:b0baa54aa17b9b41f86ce281775c9b112ff280dd744f9c542f98ea27bdc88389", "created_at": "2026-11-01T18:15:13Z", "updated_at": "2026-11-01T22:07:24Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification of an immune-related gene signature as a prognostic target and the immune microenvironment for adrenocortical carcinoma.", "doi": "10.1002/iid3.680", "pmid": "36039643", "authors": ["Chengdang Xu", "Caipeng Qin", "Jingang Jian", "Yun Peng", "Xinan Wang", "Xi Chen", "Denglong Wu", "Yuxuan Song"], "journal": "Immunity, inflammation and disease", "year": 2022, "abstract": "BACKGROUND: Adrenocortical carcinoma (ACC) is a rare endocrine malignancy. Even with complete tumor resection and adjuvant therapies, the prognosis of patients with ACC remains unsatisfactory. In the microtumor environment, the impact of a disordered immune system and abnormal immune responses is enormous. To improve treatment, novel prognostic predictors and treatment targets for ACC need to be identified. Hence, credible prognostic biomarkers of immune-associated genes (IRGs) should be explored and developed.\nMATERIAL AND METHODS: We downloaded RNA-sequencing data and clinical data from The Cancer Genome Atlas (TCGA) data set, Genotype-Tissue Expression data set, and Gene Expression Omnibus data set. Gene set enrichment analysis (GSEA) was applied to reveal the potential functions of differentially expressed genes.\nRESULTS: GSEA indicated an association between ACC and immune-related functions. We obtained 332 IRGs and constructed a prognostic signature on the strength of 3 IRGs (INHBA, HELLS, and HDAC4) in the training cohort. The high-risk group had significantly poorer overall survival than the low-risk group (p < .001). Multivariate Cox regression was performed with the signature as an independent prognostic indicator for ACC. The testing cohort and the entire TCGA ACC cohort were utilized to validate these findings. Moreover, external validation was conducted in the GSE10927 and GSE19750 cohorts. The tumor-infiltrating immune cells analysis indicated that the quantity of T cells, natural killer cells, macrophage cells, myeloid dendritic cells, and mast cells in the immune microenvironment differed between the low-risk and high-risk groups.\nCONCLUSION: Our three-IRG prognostic signature and the three IRGs can be used as prognostic indicators and potential immunotherapeutic targets for ACC. Inhibitors of the three novel IRGs might activate immune cells and play a synergistic role in combination therapy with immunotherapy for ACC in the future.", "claims": [{"id": "claim-method", "statement": "To assess the influences of the IRG prognostic signature on OS and other clinical features, Cox regression analyses, log‐rank test, and KM method were used.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36039643", "locator": "sections[9] \"Statistical analysis\" paragraph 2", "quote": "To assess the influences of the IRG prognostic signature on OS and other clinical features, Cox regression analyses, log‐rank test, and KM method were used."}], "state": "complete"}, {"id": "claim-data-access", "statement": "All data were extracted from public databases: TCGA ACC data set (http://portal.gdc.cancer.gov/), GTEx database (http://www.gtexportal.org/home/index.html), and GEO database (http://www.ncbi.nlm.nih.gov/geo/).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36039643", "locator": "sections[30] \"DATA AVAILABILITY STATEMENT\" paragraph 2", "quote": "All data were extracted from public databases: TCGA ACC data set (http://portal.gdc.cancer.gov/), GTEx database (http://www.gtexportal.org/home/index.html), and GEO database (http://www.ncbi.nlm.nih.gov/geo/)."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The high‐risk group had significantly poorer overall survival than the low‐risk group (p < .001).", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:36039643", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "The high‐risk group had significantly poorer overall survival than the low‐risk group (p < .001)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The high‐risk group had significantly poorer overall survival than the low‐risk group (p < .001).", "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:36039643"], "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:GSE10927"], "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:GSE10927"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:36039643", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1002/iid3.680", "sha256": "sha256:745edd81c851ed95df053d1143196320b9abfe2ca51402012eb9e0a89f153689", "bytes": 45862, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1002/iid3.680", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC9382862", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE10927", "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=GSE10927", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE10927", "version": null, "note": "All data were extracted from public databases: TCGA ACC data set (http://portal.gdc.cancer.gov/), GTEx database (http://www.gtexportal.org/home/index.html), and GEO database (http://www.ncbi.nlm.nih.gov/geo/).", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "All data were extracted from public databases: TCGA ACC data set (http://portal.gdc.cancer.gov/), GTEx database (http://www.gtexportal.org/home/index.html), and GEO database (http://www.ncbi.nlm.nih.gov/geo/).", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM277090", "GSM277091", "GSM277092", "GSM277093", "GSM277094", "GSM277095", "GSM277096", "GSM277097", "GSM277098", "GSM277099", "GSM277100", "GSM277101", "GSM277102", "GSM277103", "GSM277104", "GSM277105", "GSM277106", "GSM277107", "GSM277108", "GSM277109", "GSM277110", "GSM277111", "GSM277112", "GSM277113", "GSM277114", "GSM277115", "GSM277116", "GSM277117", "GSM277118", "GSM277119", "GSM277120", "GSM277121", "GSM277122", "GSM277123", "GSM277124", "GSM277125", "GSM277126", "GSM277127", "GSM277128", "GSM277129", "GSM277130", "GSM277131", "GSM277132", "GSM277133", "GSM277134", "GSM277135", "GSM277136", "GSM277137", "GSM277138", "GSM277139", "GSM277140", "GSM277141", "GSM277142", "GSM277143", "GSM277144", "GSM277145", "GSM277146", "GSM277147", "GSM277148", "GSM277149", "GSM277150", "GSM277151", "GSM277152", "GSM277153", "GSM277154"], "sample_count": 65, "group_sizes": null, "group_sizes_basis": null, "platform": "570", "taxon": "Homo sapiens", "title": "Human adrenocortical carcinomas (33), adenomas (22), and normal adrenal cortex (10), on Affymetrix HG_U133_plus_2 arrays", "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:GSE19750", "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=GSE19750", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE19750", "version": null, "note": "All data were extracted from public databases: TCGA ACC data set (http://portal.gdc.cancer.gov/), GTEx database (http://www.gtexportal.org/home/index.html), and GEO database (http://www.ncbi.nlm.nih.gov/geo/).", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "All data were extracted from public databases: TCGA ACC data set (http://portal.gdc.cancer.gov/), GTEx database (http://www.gtexportal.org/home/index.html), and GEO database (http://www.ncbi.nlm.nih.gov/geo/).", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM1094056", "GSM1094057", "GSM1094058", "GSM1094059", "GSM1094060", "GSM1094061", "GSM1094062", "GSM1094063", "GSM1094064", "GSM1094065", "GSM1094066", "GSM1094067", "GSM1094068", "GSM1094069", "GSM1094070", "GSM1094071", "GSM1094072", "GSM1094073", "GSM1094074", "GSM1094075", "GSM1094076", "GSM1094077", "GSM1094078", "GSM1094079", "GSM1094080", "GSM493251", "GSM493252", "GSM493253", "GSM493254", "GSM493255", "GSM493256", "GSM493257", "GSM493258", "GSM493259", "GSM493260", "GSM493261", "GSM493262", "GSM493263", "GSM493264", "GSM493265", "GSM493266", "GSM493267", "GSM493268", "GSM493269", "GSM493270", "GSM493271", "GSM493272", "GSM493273"], "sample_count": 48, "group_sizes": null, "group_sizes_basis": null, "platform": "570", "taxon": "Homo sapiens", "title": "Adrenocortical Carcinoma Gene Expression Profiling [Affymetrix]", "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:GSE10927 not downloaded", "asset:data:geo:GSE10927 licence not read", "asset:data:geo:GSE19750 not downloaded", "asset:data:geo:GSE19750 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": 1.0, "band": "verbatim", "quote": "To assess the influences of the IRG prognostic signature on OS and other clinical features, Cox regression analyses, log‐rank test, and KM method were used."}}, {"id": "method-2", "family": "group_comparison", "specific": "student_t_test", "label": "Group comparison", "dsl_operations": [], "missing_operations": ["student_t"], "expressible": false, "parameters": {}, "data_shapes": ["two_or_more_groups_continuous"], "evidence": {"score": 0.8, "band": "high", "quote": "Student's t test"}}, {"id": "method-3", "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": 0.8, "band": "high", "quote": "KM"}}, {"id": "method-4", "family": "diagnostic_evaluation", "specific": "roc", "label": "Diagnostic test evaluation", "dsl_operations": ["confusion_counts", "roc_curve", "sensitivity_specificity", "solve_confusion_matrix", "classification_metrics", "published_precision_envelope"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["reference_standard_and_test"], "evidence": {"score": 0.8, "band": "high", "quote": "ROC curve"}}, {"id": "method-5", "family": "contingency_analysis", "specific": "chi_square", "label": "Categorical (contingency table) analysis", "dsl_operations": ["chi_square_test"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["categorical_cross_tabulation"], "evidence": {"score": 0.8, "band": "high", "quote": "χ 2"}}], "targets": [], "gaps": ["method.reader_differs_from_extractor"]}, "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": ["GSE10927", "GSE19750"], "resolved_accessions": ["GSE10927", "GSE19750"], "statements": ["All data were extracted from public databases: TCGA ACC data set (http://portal.gdc.cancer.gov/), GTEx database (http://www.gtexportal.org/home/index.html), and GEO database (http://www.ncbi.nlm.nih.gov/geo/)."], "basis": "The paper names GSE10927, GSE19750 in Gene Expression Omnibus (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:36039643", "data:geo:GSE10927"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE10927"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T18:02:35Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 13316, "completion_tokens": 1863, "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:36039643", "type": "paper", "label": "pmid:36039643"}, {"id": "source:pmid:36039643", "type": "manuscript", "label": "PMID 36039643 full text"}, {"id": "data:geo:GSE10927", "type": "dataset", "label": "GEO GSE10927"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:36039643", "type": "paper", "label": "pmid:36039643"}, {"id": "source:pmid:36039643", "type": "manuscript", "label": "PMID 36039643 full text"}, {"id": "data:geo:GSE10927", "type": "dataset", "label": "GEO GSE10927"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-36039643", "type": "extraction", "used": ["source:pmid:36039643"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE10927", "type": "accession_resolution", "used": ["data:geo:GSE10927"], "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:36039643", "parent_hash": "sha256:80937f0627ad32c7d898618ee4e1b8c073acb189761de4be17622140ad9c86ec", "fork_of": null, "generation": 3}, "gaps": ["asset:data:geo:GSE10927 licence not read", "asset:data:geo:GSE10927 not downloaded", "asset:data:geo:GSE19750 licence not read", "asset:data:geo:GSE19750 not downloaded", "execution.not_run", "method.reader_differs_from_extractor", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"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": ["To assess the influences of the IRG prognostic signature on OS and other clinical features, Cox regression analyses, log‐rank test, and KM method were used."], "order_basis": "analysis_only", "id": "assay:1"}]}