Intrinsic Genomic Differences Between African American and White Patients With Clear Cell Renal Cell Carcinoma.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:27010573", "kind": "science-record", "revision": 6, "content_hash": "sha256:8d1bf5a6d8e150382349bafdcc2963ac20355459039aaba6e714126d5e81ad4e", "created_at": "2026-11-01T15:40:17Z", "updated_at": "2026-11-01T21:20:29Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Intrinsic Genomic Differences Between African American and White Patients With Clear Cell Renal Cell Carcinoma.", "doi": "10.1001/jamaoncol.2016.0005", "pmid": "27010573", "authors": ["Bhavani Krishnan", "Tracy L Rose", "Jordan Kardos", "Matthew I Milowsky", "William Y Kim"], "journal": "JAMA oncology", "year": 2016, "abstract": "IMPORTANCE: There are well-documented racial disparities in outcomes for African American patients with clear cell renal cell carcinoma (ccRCC). Despite a dramatic improvement in overall survival in white patients since the advent of targeted therapy, survival for African Americans with advanced ccRCC has not changed. There is little known about potential racial differences in tumor biology of ccRCC.\nOBJECTIVE: To determine if there are racial differences in the somatic mutation rate and gene expression of ccRCC tumors from white and African American patients.\nDESIGN, SETTING, AND PARTICIPANTS: Overall, 438 patients with ccRCC were identified through The Cancer Genome Atlas (TCGA) clear cell kidney (KIRC) dataset (419 white and 19 African American patients). The GSE25540 dataset containing 135 patients (125 white and 10 African American patients) was used for validation. Tumor samples were collected from numerous cancer centers and were examined for racial differences in somatic mutation rates and RNA expression. Racial differences in somatic mutation rates and RNA expression were examined.\nMAIN OUTCOMES AND MEASURES: The comparison of somatic mutation rates and differences in RNA expression in white and African American patients with ccRCC.\nRESULTS: Overall, 419 ccRCC tumor data sets from non-Hispanic white patients and 19 from non-Hispanic African American patients were identified through the publically available TCGA KIRC data set, and a validation set of 125 white and 10 African American ccRCC patient tumors was identified from the publicly available GSE25540 data set. African American patients were significantly less likely than white patients to have VHL mutations (2 of 12 [17%] vs 175 of 351 [50%], respectively; P = .04) and were enriched in the ccB molecular subtype (79% in African American vs 45% in white patients ; P = .005), a molecular subtype that carries a worse prognosis. It was found that RNA expression analysis revealed relative down-regulation of hypoxia-inducible factor (HIF) and vascular endothelial growth factor (VEGF)-associated pathways in African American patients compared with white patients.\nCONCLUSIONS AND RELEVANCE: African American patients have less frequent VHL inactivation, are enriched in the ccB molecular subtype, and have decreased up-regulation of HIF-associated gene signatures than white patients. These genomic differences would predict decreased responsiveness to VEGF-targeted therapy and are a biologically plausible contributing factor to the worse survival of African American patients with ccRCC, even in the targeted therapy era.", "claims": [{"id": "claim-target-result", "statement": "Using χ² or Fisher exact tests to compare somatic mutation rates in TCGA KIRC data, with validation in GSE25540, the study found that African American ccRCC tumors had less frequent VHL inactivation, enrichment for the ccB subtype, and lower HIF/VEGF pathway activation than tumors from white patients.", "kind": "quantitative", "target": {"value": 5.0, "unit": "p-value", "tolerance": null, "source": "Classification of the TCGA KIRC tumors into ccA and ccB subtypes showed that African Americans had significant enrichment for the ccB subtype (15 of 19 [79%] African American patients have the ccB subtype compared with 190 of 419 [45%] white patients; P = 005)"}, "evidence": [{"asset": "source:pmid:27010573", "locator": "sections[0] \"Abstract\" paragraph 5", "quote": "Overall, 419 ccRCC tumor data sets from non-Hispanic white patients and 19 from non-Hispanic African American patients were identified through the publically available TCGA KIRC data set, and a validation set of 125 white and 10 African American ccRCC patient tumors was identified from the publicly available GSE25540 data set."}, {"asset": "source:pmid:27010573", "locator": "sections[6] \"Results\" paragraph 2", "quote": "Overall, 175 of 351 (50%) white patients had VHL mutations, whereas 2 of 12 (17%) African American patients had VHL mutations (P = .04)"}, {"asset": "source:pmid:27010573", "locator": "sections[6] \"Results\" paragraph 4", "quote": "Classification of the TCGA KIRC tumors into ccA and ccB subtypes showed that African Americans had significant enrichment for the ccB subtype (15 of 19 [79%] African American patients have the ccB subtype compared with 190 of 419 [45%] white patients; P = 005)"}, {"asset": "source:pmid:27010573", "locator": "sections[0] \"Abstract\" paragraph 6", "quote": "African American patients have less frequent VHL inactivation, are enriched in the ccB molecular subtype, and have decreased up-regulation of HIF-associated gene signatures than white patients."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "Using χ² or Fisher exact tests to compare somatic mutation rates in TCGA KIRC data, with validation in GSE25540, the study found that African American ccRCC tumors had less frequent VHL inactivation, enrichment for the ccB subtype, and lower HIF/VEGF pathway activation than tumors from white 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:27010573"], "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": "blocked", "blocked_on": "data:accession_absent", "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": [], "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": [], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": ["step:obtain_source_data blocked on data:accession_absent"]}, "data": {"state": "partial", "assets": [{"id": "source:pmid:27010573", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1001/jamaoncol.2016.0005", "sha256": "sha256:650d2f4365771aaaa2136950d064cabef463eadcdbbdfac1b7b32fe00b3bac39", "bytes": 12766, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1001/jamaoncol.2016.0005", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC5035632", "source": "ncbi_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}], "gaps": []}, "analysis": {"state": "complete", "methods": [{"id": "method-1", "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": "χ2"}}], "targets": [{"id": "target-published-estimate", "claim_id": "claim-target-result", "operation": "chi_square_test", "expected_value": 5.0, "unit": "p-value", "tolerance": null, "state": "complete", "note": "The threshold the paper applied to its own result, as the paper states it. A run that reproduces the effect is judged against this threshold."}], "gaps": []}, "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": "blocked", "tier": "R4", "blocking_axis": "data", "blocked_on": "data:accession_absent", "axes": {"method": {"tier": "R1", "expressible": true, "required_operations": ["chi_square_test"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: chi_square."}, "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": "R4", "reachable": false, "accessions": [], "resolved_accessions": [], "statements": [], "basis": "The paper names no accession to its source data, so the data has to come from the authors."}}, "can_run": {"dsl_operations": ["chi_square_test"], "assets": ["source:pmid:27010573"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:None"]}, "gaps": ["data:accession_absent"]}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-10-31T18:28:01Z", "independence": "single_reader"}, "evidence_check": {"method": null, "availability": null}, "calls": 2, "usage": {"prompt_tokens": 6519, "completion_tokens": 1196, "cached_tokens": 528}}, "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:27010573", "type": "paper", "label": "pmid:27010573"}, {"id": "source:pmid:27010573", "type": "manuscript", "label": "PMID 27010573 full text"}, {"id": "data:geo:None", "type": "dataset", "label": "GEO None"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:27010573", "type": "paper", "label": "pmid:27010573"}, {"id": "source:pmid:27010573", "type": "manuscript", "label": "PMID 27010573 full text"}, {"id": "data:geo:None", "type": "dataset", "label": "GEO None"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-27010573", "type": "extraction", "used": ["source:pmid:27010573"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-None", "type": "accession_resolution", "used": ["data:geo:None"], "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:27010573", "parent_hash": "sha256:6322ea2ade71b4c5a37bdcc6a648b3f6a4b1d71b350810c1286674ecbcdf6175", "fork_of": null, "generation": 5}, "gaps": ["execution.not_run", "review.human_critique", "review.independent_reader", "review.machine_critique", "step:obtain_source_data blocked on data:accession_absent"], "assays": [{"role": "analysis", "definition_id": "contingency_analysis", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["chi_square_test"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 0.8, "evidence": ["χ2"], "order_basis": "analysis_only", "id": "assay:1"}]}