Identification and validation of a combined hypoxia and immune index for triple-negative breast cancer.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:32521117", "kind": "science-record", "revision": 8, "content_hash": "sha256:c22a7386f442c0af3b3e57014ee340bc4d4a2ae03d8aea01687a98892b9e7178", "created_at": "2026-11-01T15:41:03Z", "updated_at": "2026-11-01T22:01:44Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification and validation of a combined hypoxia and immune index for triple-negative breast cancer.", "doi": "10.1002/1878-0261.12747", "pmid": "32521117", "authors": ["Shaoquan Zheng", "Yutian Zou", "Jie-Ying Liang", "Weikai Xiao", "Anli Yang", "Tiebao Meng", "Shilin Lu", "Zhongbing Luo", "Xiaoming Xie"], "journal": "Molecular oncology", "year": 2020, "abstract": "The interaction between hypoxia and immune status has been confirmed in various cancer settings, and corresponding treatments have been investigated. However, reliable biomarkers are needed for individual treatment, so we sought to develop a novel scoring system based on hypoxia and immune status. Prognostic hypoxia-immune status-related signatures of patients with triple-negative breast cancer (TNBC) were identified in The Cancer Genome Atlas (TCGA) (N = 158), Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) (N = 297), and GSE58812 (N = 107). LASSO Cox regression was used for model construction. Hypoxia and immune status expression profiles were analyzed, and infiltrating immune cells were compared. Quantitative real-time PCR (qRT-PCR) was used for validation in the Sun Yat-sen University Cancer Center (SYSUCC) cohort, and immunofluorescence was applied for the detection of hypoxia and immune markers in cancer tissues. Ten cross-cohort prognostic hypoxia-immune signatures were included to construct the comprehensive index of hypoxia and immune (CIHI) in the METABRIC cohort. Two subgroups of patients with distinct hypoxia-immune status conditions were identified using CIHI: hypoxiahigh /immunelow and hypoxialow /immunehigh , with a significantly better overall survival (OS) rate in the latter (P < 0.01). The prognostic value of CIHI was further validated in the TCGA, GSE58812, and SYSUCC cohorts (P < 0.01). Hypoxia-immune signatures were significantly differentially expressed between the two groups, and more active immune responses were observed in the hypoxialow /immunehigh group. Cytotoxic lymphocytes were inversely correlated with CIHI in silico. Differentially expressed CA-IX and stromal PD-L1 were detected between subgroups of the SYSUCC cohort. A hypoxia-immune-based cross-cohort classifier for predicting prognosis was developed and validated, which may guide hypoxia modifier treatment and immunotherapy for TNBC.", "claims": [{"id": "claim-data-access", "statement": "The METABRIC data were obtained from cBioportal (http://www.cbioportal.org/) [25].", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:32521117", "locator": "sections[4] \"Study population and data acquisition\" paragraph 4", "quote": "The METABRIC data were obtained from cBioportal (http://www.cbioportal.org/) [25]."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": null, "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:32521117"], "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:GSE58812"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "blocked", "blocked_on": "method:group_comparison_wilcoxon", "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:GSE58812"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": ["step:run_analysis blocked on method:group_comparison_wilcoxon"]}, "data": {"state": "partial", "assets": [{"id": "source:pmid:32521117", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1002/1878-0261.12747", "sha256": "sha256:d058955b2f81d2e2634edcd8ad14f925efea7a5285c6f9c08cd466e618dd1398", "bytes": 64146, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1002/1878-0261.12747", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC7607163", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE58812", "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=GSE58812", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE58812", "version": null, "note": "The METABRIC data were obtained from cBioportal (http://www.cbioportal.org/) [25].", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The METABRIC data were obtained from cBioportal (http://www.cbioportal.org/) [25].", "access_statement_kind": "repository_route_statement", "sample_accessions": ["GSM1419942", "GSM1419943", "GSM1419944", "GSM1419945", "GSM1419946", "GSM1419947", "GSM1419948", "GSM1419949", "GSM1419950", "GSM1419951", "GSM1419952", "GSM1419953", "GSM1419954", "GSM1419955", "GSM1419956", "GSM1419957", "GSM1419958", "GSM1419968", "GSM1419969", "GSM1419970", "GSM1419971", "GSM1419972", "GSM1419973", "GSM1419974", "GSM1419975", "GSM1419976", "GSM1419977", "GSM1419978", "GSM1419979", "GSM1419980", "GSM1419981", "GSM1419982", "GSM1419983", "GSM1419984", "GSM1419985", "GSM1419986", "GSM1419987", "GSM1419988", "GSM1419989", "GSM1419990", "GSM1419991", "GSM1419992", "GSM1419993", "GSM1419994", "GSM1419995", "GSM1419996", "GSM1419997", "GSM1419998", "GSM1419999", "GSM1420000", "GSM1420001", "GSM1420002", "GSM1420003", "GSM1420004", "GSM1420005", "GSM1420006", "GSM1420007", "GSM1420008", "GSM1420009", "GSM1420010", "GSM1420011", "GSM1420012", "GSM1420013", "GSM1420014", "GSM1420015", "GSM1420016", "GSM1420017", "GSM1420018", "GSM1420019", "GSM1420020", "GSM1420021", "GSM1420022", "GSM1420023", "GSM1420024", "GSM1420025", "GSM1420026", "GSM1420027", "GSM1420028", "GSM1420029", "GSM1420030", "GSM1420031", "GSM1420032", "GSM1420033", "GSM1420034", "GSM1420035", "GSM1420036", "GSM1420037", "GSM1420038", "GSM1420039", "GSM1420040", "GSM1420041", "GSM1420042", "GSM1420043", "GSM1420044", "GSM1420045", "GSM1420046", "GSM1420047", "GSM1420048", "GSM1420049", "GSM1420050", "GSM1420051", "GSM1420052", "GSM1420053", "GSM1420054", "GSM1420055", "GSM1420056", "GSM1420057"], "sample_count": 107, "group_sizes": null, "group_sizes_basis": null, "platform": "570", "taxon": "Homo sapiens", "title": "Gene-expression molecular subtyping of triple-negative breast cancer tumours: importance of immune response", "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:SRP157974", "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=SRP157974", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "SRP157974", "version": null, "note": "The METABRIC data were obtained from cBioportal (http://www.cbioportal.org/) [25].", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The METABRIC data were obtained from cBioportal (http://www.cbioportal.org/) [25].", "access_statement_kind": "repository_route_statement", "sample_accessions": [], "sample_count": null, "group_sizes": null, "group_sizes_basis": null, "platform": null, "taxon": null, "title": null, "resolution_checked_at": "2026-10-31T18:35:43Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}], "gaps": ["asset:data:geo:GSE58812 not downloaded", "asset:data:geo:GSE58812 licence not read", "asset:data:geo:SRP157974 not downloaded", "asset:data:geo:SRP157974 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "family": "group_comparison", "specific": "wilcoxon", "label": "Group comparison", "dsl_operations": [], "missing_operations": ["group_comparison_wilcoxon"], "expressible": false, "parameters": {}, "data_shapes": ["two_or_more_groups_continuous"], "evidence": {"score": 0.8, "band": "high", "quote": "Wilcoxon"}}, {"id": "method-2", "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-3", "family": "model_calibration", "specific": "decision_curve", "label": "Model calibration / clinical utility", "dsl_operations": ["calibration_bins", "net_benefit"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["predictions_and_outcomes"], "evidence": {"score": 0.8, "band": "high", "quote": "Decision curve analysis"}}], "targets": [], "gaps": ["method.group_comparison_wilcoxon"]}, "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": false, "required_operations": [], "missing_operations": ["group_comparison_wilcoxon"], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: wilcoxon."}, "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": ["SRP157974", "GSE58812"], "resolved_accessions": ["GSE58812"], "statements": ["The METABRIC data were obtained from cBioportal (http://www.cbioportal.org/) [25]."], "basis": "The paper names GSE58812 in Sequence Read Archive (SRA) and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": [], "assets": ["source:pmid:32521117", "data:geo:GSE58812"], "steps": []}, "must_build": {"dsl_operations": [{"operation": "group_comparison_wilcoxon", "unlocks_papers": null, "priority": null}], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE58812"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-10-31T19:03:53Z", "independence": "single_reader"}, "evidence_check": {"method": null, "availability": null}, "calls": 3, "usage": {"prompt_tokens": 48959, "completion_tokens": 2378, "cached_tokens": 784}}, "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:32521117", "type": "paper", "label": "pmid:32521117"}, {"id": "source:pmid:32521117", "type": "manuscript", "label": "PMID 32521117 full text"}, {"id": "data:geo:GSE58812", "type": "dataset", "label": "GEO GSE58812"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:32521117", "type": "paper", "label": "pmid:32521117"}, {"id": "source:pmid:32521117", "type": "manuscript", "label": "PMID 32521117 full text"}, {"id": "data:geo:GSE58812", "type": "dataset", "label": "GEO GSE58812"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-32521117", "type": "extraction", "used": ["source:pmid:32521117"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE58812", "type": "accession_resolution", "used": ["data:geo:GSE58812"], "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:32521117", "parent_hash": "sha256:d1bded5aa0b96f816e86b2c0bfb3cb368a21f6d6e13a5afcbfb7ba03fc8c0008", "fork_of": null, "generation": 7}, "gaps": ["asset:data:geo:GSE58812 licence not read", "asset:data:geo:GSE58812 not downloaded", "asset:data:geo:SRP157974 licence not read", "asset:data:geo:SRP157974 not downloaded", "execution.not_run", "method.group_comparison_wilcoxon", "review.human_critique", "review.independent_reader", "review.machine_critique", "step:run_analysis blocked on method:group_comparison_wilcoxon"], "assays": [{"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": ["ing immune cells were compared. Quantitative real-time PCR (qRT-PCR) was used for validation in the Sun"], "order_basis": "paper_text_order:805", "id": "assay:1"}, {"role": "data_generation", "definition_id": "ihc", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["niversity Cancer Center (SYSUCC) cohort, and immunofluorescence was applied for the detection of hypoxia and"], "order_basis": "paper_text_order:918", "id": "assay:2"}, {"role": "analysis", "definition_id": "group_comparison", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 0.8, "evidence": ["Wilcoxon"], "order_basis": "consumes_earlier_output", "id": "assay:3"}]}