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pmid:39044302
Prostate cancers with distinct transcriptional programs in Black and White men.
Minhyung Kim · Patrick Tamukong · Gloria Cecilia Galvan · Qian Yang · Amanda De Hoedt · Michael R Freeman · Sungyong You · Stephen Freedland
Genome medicine · 2024 doi:10.1186/s13073-024-01361-0
Paper
complete
Experiment
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Data
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Analysis
partial
Execution
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Complete file
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This study aimed to identify differential transcriptional regulation between Black and White men with PC.\nMETHODS: We performed microarray of radical prostatectomy tissue blocks from 305 Black and 238 White men treated at the Durham Veterans Affairs Medical Center. Differential expression, gene set enrichment analysis, master regulator analysis, and network modeling were conducted to compare gene expression by race. Findings were validated using external datasets that are available in the Gene Expression Omnibus (GEO) database. The first was a multi-institutional cohort of 1152 prostate cancer patients (596 Black, 556 White) with microarray data (GEO ID: GSE169038). The second was an Emory cohort of 106 patients (22 Black, 48 White, 36 men of unknown race) with RNA-seq data (GEO ID: GSE54460). Additionally, we analyzed androgen receptor (AR) chromatin binding profiles using paired AR ChIP-Seq datasets from Black and White men (GEO IDs: GSE18440 and GSE18441).\nRESULTS: We identified 871 differentially expressed genes between Black and White men. White men had higher activity of MYC-related pathways, while Black men showed increased activity of inflammation, steroid hormone responses, and cancer progression-related pathways. We further identified the top 10 transcription factors (TFs) in Black patients, which formed a transcriptional regulatory network centered on the AR. The activities of this network and the pathways were significantly different in Black vs. White men across multiple cohorts and PC molecular subtypes.\nCONCLUSIONS: These findings suggest PC in Black and White men have distinct tumor transcriptional profiles. Furthermore, a highly interactive TF network centered on AR drives differential gene expression in Black men. Additional study is needed to understand the degree to which these differences in transcriptional regulatory elements contribute to PC health disparities.", "claims": [{"id": "claim-method", "statement": "Genes with significant differential expression between Black and White men were identified using the integrated hypothesis testing method as previously reported.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39044302", "locator": "sections[5] \"Differential expression analysis of PCs from Black and White men\" paragraph 2", "quote": "Genes with significant differential expression between Black and White men were identified using the integrated hypothesis testing method as previously reported."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The transcriptome data of the DVAHCS cohort is available under controlled access from Decipher (http://decipher.sanger.ac.uk). 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"GSM1323748", "GSM1323749", "GSM1323750", "GSM1323751", "GSM1323752"], "sample_count": 106, "group_sizes": null, "group_sizes_basis": null, "platform": "11154", "taxon": "Homo sapiens", "title": "RNAseq Analysis of Formalin-Fixed Paraffin-Embedded Prostate Cancer Tissues", "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:GSE169038 not downloaded", "asset:data:geo:GSE169038 licence not read", "asset:data:geo:GSE18440 not downloaded", "asset:data:geo:GSE18440 licence not read", "asset:data:geo:GSE18441 not downloaded", "asset:data:geo:GSE18441 licence not read", "asset:data:geo:GSE54460 not downloaded", "asset:data:geo:GSE54460 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "family": "group_comparison", "specific": "wilcoxon", "label": "Group comparison", "dsl_operations": [], "missing_operations": 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[]}, "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": ["GSE169038", "GSE54460", "GSE18440", "GSE18441"], "resolved_accessions": ["GSE169038", "GSE54460", "GSE18440", "GSE18441"], "statements": ["The transcriptome data of the DVAHCS cohort is available under controlled access from Decipher (http://decipher.sanger.ac.uk). The transcriptome data used for validation and the AR ChIP-Seq data were acquired from publicly available at Gene Expression Omnibus (GEO) (https://www.ncbi.nlm.nih.gov/geo/): GSE169038 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE169038) [16], GSE54460 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE54460) [17], GSE18440 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE18440) [71], and GSE18441 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE18441) [72]."], "basis": "The paper names GSE169038, GSE54460, GSE18440, GSE18441 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": [], "assets": ["source:pmid:39044302", "data:geo:GSE169038"], "steps": []}, "must_build": {"dsl_operations": [{"operation": "group_comparison_wilcoxon", "unlocks_papers": null, "priority": null}], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE169038"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T19:24:47Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 11750, "completion_tokens": 2255, "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:39044302", "type": "paper", "label": "pmid:39044302"}, {"id": "source:pmid:39044302", "type": "manuscript", "label": "PMID 39044302 full text"}, {"id": "data:geo:GSE169038", "type": "dataset", "label": "GEO GSE169038"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:39044302", "type": "paper", "label": "pmid:39044302"}, {"id": "source:pmid:39044302", "type": "manuscript", "label": "PMID 39044302 full text"}, {"id": "data:geo:GSE169038", "type": "dataset", "label": "GEO GSE169038"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-39044302", "type": "extraction", "used": ["source:pmid:39044302"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE169038", "type": "accession_resolution", "used": ["data:geo:GSE169038"], "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:39044302", "parent_hash": "sha256:cf04f33060f12f2cdbc8366918b707994c1695623f674e10f371532d5f09f0b8", "fork_of": null, "generation": 2}, "gaps": ["asset:data:geo:GSE169038 licence not read", "asset:data:geo:GSE169038 not downloaded", "asset:data:geo:GSE18440 licence not read", "asset:data:geo:GSE18440 not downloaded", "asset:data:geo:GSE18441 licence not read", "asset:data:geo:GSE18441 not downloaded", "asset:data:geo:GSE54460 licence not read", "asset:data:geo:GSE54460 not downloaded", "execution.not_run", "method.group_comparison_wilcoxon", "method.reader_named_unmapped", "review.human_critique", "review.independent_reader", "review.machine_critique", "step:run_analysis blocked on method:group_comparison_wilcoxon"], "assays": [{"role": "data_generation", "definition_id": "microarray", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["and White men with PC. METHODS: We performed microarray of radical prostatectomy tissue blocks from", "cancer patients (596 Black, 556 White) with microarray data (GEO ID: GSE169038). The second was an", "Methods Sample preparation and microarray data from the DVAHCS cohort As previously de", "SA). RNA extraction, cDNA amplification, and microarray hybridization were performed as previously d"], "order_basis": "paper_text_order:319", "id": "assay:1"}, {"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": ["lack, 48 White, 36 men of unknown race) with RNA-seq data (GEO ID: GSE54460). Additionally, we an"], "order_basis": "paper_text_order:963", "id": "assay:2"}, {"role": "data_generation", "definition_id": "chip_seq", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": [") chromatin binding profiles using paired AR ChIP-Seq datasets from Black and White men (GEO IDs:", "AR chromatin immunoprecipitation sequencing (ChIP-Seq) data of Black and White men were downloaded"], "order_basis": "paper_text_order:1088", "id": "assay:3"}, {"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:4"}]}