Genomic analysis of pancreatic cancer reveals 3 molecular subtypes with different clinical outcomes.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:33832071", "kind": "science-record", "revision": 7, "content_hash": "sha256:7fcbd0551d5f6562a42ab3a6f7623f9882258d47711c7f6801fde20a2df005e0", "created_at": "2026-11-01T15:41:31Z", "updated_at": "2026-11-01T22:46:29Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Genomic analysis of pancreatic cancer reveals 3 molecular subtypes with different clinical outcomes.", "doi": "10.1097/MD.0000000000024969", "pmid": "33832071", "authors": ["Ji Woong Hwang", "Soo Kyung Jang", "Dong Jin Lee"], "journal": "Medicine", "year": 2021, "abstract": "ABSTRACT: Pancreatic cancer has a very high mortality with a 5-year survival of <5%. The purpose of this study was to classify specific molecular subtypes associated with prognosis of pancreatic cancer using The Cancer Genome Atlas (TCGA) multiplatform genomic data.Multiplatform genomic data (N = 178), including gene expression, copy number alteration, and somatic mutation data, were obtained from cancer browser (https://genome-cancer.ucsc.edu, cohort: TCGA Pancreatic Cancer). Clinical data including survival results were analyzed. We also used validation cohort (GSE50827) to confirm the robustness of these molecular subtypes in pancreatic cancer.When we performed unsupervised clustering using TCGA gene expression data, we found three distinct molecular subtypes associated with different survival results. Copy number alteration and somatic mutation data showed different genomic patterns for these three subtypes. Ingenuity pathway analysis revealed that each subtype showed differentially altered pathways. Using each subtype-specific genes (200 were selected), we could predict molecular subtype in another cohort, confirming the robustness of these molecular subtypes of pancreatic cancer. Cox regression analysis revealed that molecular subtype is the only significant prognostic factor for pancreatic cancer (P = .042, 95% confidence interval 0.523-0.98).Genomic analysis of pancreatic cancer revealed 3 distinct molecular subtypes associated with different survival results. Using these subtype-specific genes and prediction model, we could predict molecular subtype associated with prognosis of pancreatic cancer.", "claims": [{"id": "claim-method", "statement": "Association of each subtype with overall survival was evaluated using Kaplan-Meier plots and log rank test.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33832071", "locator": "sections[5] \"Survival analysis\" paragraph 2", "quote": "Association of each subtype with overall survival was evaluated using Kaplan-Meier plots and log rank test."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets generated during and/or analyzed during the current study are publicly available.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33832071", "locator": "sections[21] \"fn-group\" paragraph 1", "quote": "The datasets generated during and/or analyzed during the current study are publicly available."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "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:33832071"], "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:GSE50827"], "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:GSE50827"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:33832071", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1097/MD.0000000000024969", "sha256": "sha256:152317612d8a272532be679ca2edd7073e1cc772343eca263009371d5d394106", "bytes": 25071, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1097/MD.0000000000024969", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC8036077", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE50827", "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=GSE50827", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE50827", "version": null, "note": "The datasets generated during and/or analyzed during the current study are publicly available.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The datasets generated during and/or analyzed during the current study are publicly available.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM1230416", "GSM1230417", "GSM1230418", "GSM1230419", "GSM1230420", "GSM1230421", "GSM1230422", "GSM1230423", "GSM1230424", "GSM1230425", "GSM1230426", "GSM1230427", "GSM1230428", "GSM1230429", "GSM1230430", "GSM1230431", "GSM1230432", "GSM1230433", "GSM1230434", "GSM1230435", "GSM1230436", "GSM1230437", "GSM1230438", "GSM1230439", "GSM1230440", "GSM1230441", "GSM1230442", "GSM1230443", "GSM1230444", "GSM1230445", "GSM1230446", "GSM1230447", "GSM1230448", "GSM1230449", "GSM1230450", "GSM1230451", "GSM1230452", "GSM1230453", "GSM1230454", "GSM1230455", "GSM1230456", "GSM1230457", "GSM1230458", "GSM1230459", "GSM1230460", "GSM1230461", "GSM1230462", "GSM1230463", "GSM1230464", "GSM1230465", "GSM1230466", "GSM1230467", "GSM1230468", "GSM1230469", "GSM1230470", "GSM1230471", "GSM1230472", "GSM1230473", "GSM1230474", "GSM1230475", "GSM1230476", "GSM1230477", "GSM1230478", "GSM1230479", "GSM1230480", "GSM1230481", "GSM1230482", "GSM1230483", "GSM1230484", "GSM1230485", "GSM1230486", "GSM1230487", "GSM1230488", "GSM1230489", "GSM1230490", "GSM1230491", "GSM1230492", "GSM1230493", "GSM1230494", "GSM1230495", "GSM1230496", "GSM1230497", "GSM1230498", "GSM1230499", "GSM1230500", "GSM1230501", "GSM1230502", "GSM1230503", "GSM1230504", "GSM1230505", "GSM1230506", "GSM1230507", "GSM1230508", "GSM1230509", "GSM1230510", "GSM1230511", "GSM1230512", "GSM1230513", "GSM1230514", "GSM1230515", "GSM1230516", "GSM1230517", "GSM1230518"], "sample_count": 103, "group_sizes": null, "group_sizes_basis": null, "platform": "10558", "taxon": "Homo sapiens", "title": "ICGC Pancreas: Genomewide DNA methylation patterns in pancreatic ductal adenocarcinoma (gene expression of 103 samples)", "resolution_checked_at": "2026-11-01T15:39:54Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "asset:table:pmid:33832071:1", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:4a731a7c10accb5d92d3119043c56fddfc9486712b36e3d5a571c6948f673a52", "bytes": 760, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[17]/table-wrap[1]#T3", "version": null, "note": "Uivariate and multivariate analysis of clinicopathologic factors and gene signatures using Cox regression analysis.", "structure": {"pmcid": "PMC8036077", "section_index": 10, "section_title": "Cox regression analysis and hazard ratio of each clinical variable and gene signatures", "row_count": 10, "column_count": 5}, "table": {"label": "Table 3", "caption": "Uivariate and multivariate analysis of clinicopathologic factors and gene signatures using Cox regression analysis.", "rows": [["Factors", "Exp (β)", "SE", "95.0% CI", "P"], ["Univariate analysis"], ["Gene signatures", "0.707", "0.150", "(0.526–0.948)", ".021∗"], ["Sex (male)", "0.894", "0.221", "(0.579–1.38)", ".61"], ["Node-positive", "2.031", "0.274", "(1.186–3.476)", ".0098∗"], ["Stage IV", "4.101", "1.007", "(0.569–29.53)", ".161"], ["T4", "1.613", "1.226", "(0.145–17.8)", ".697"], ["Multivariate analysis"], ["Gene signatures", "0.719", "1.39", "(0.523–0.98)", ".042∗"], ["Node-positive", "1.04", "0.8669", "(0.190–5.690)", ".963"]], "row_count": 10, "column_count": 5, "numeric_cells": 29, "header_rows": 1, "locator": "section[17]/table-wrap[1]#T3"}}, {"id": "asset:table:pmid:33832071:2", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:acb0f2110faf04bfe22f9747572fcdc7fe9e7176ccd586f6904351baed8d636e", "bytes": 1302, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[12]/table-wrap[1]#T1", "version": null, "note": "Case distribution according to each cluster after unsupervised clustering of The Cancer Genome Atlas Pancreatic cancers (N = 178).", "structure": {"pmcid": "PMC8036077", "section_index": 12, "section_title": "Analysis of TCGA genomic data showed novel molecular subtypes of pancreatic cancer associated with clinical behavior", "row_count": 31, "column_count": 6}, "table": {"label": "Table 1", "caption": "Case distribution according to each cluster after unsupervised clustering of The Cancer Genome Atlas Pancreatic cancers (N = 178).", "rows": [["", "Cluster 1 (N = 71)", "Cluster 2 (N = 69)", "Cluster 3 (N = 38)", "Total (N = 178)", "P"], ["Mean age, y", "66.3", "64.7", "61.7", "", ""], ["Sex", "", "", "", "", ".549"], ["Male", "34", "38", "19", "91", ""], ["Female", "29", "28", "17", "74", ""], ["NA", "8", "3", "2", "13", ""], ["Stage", "", "", "", "", ".065"], ["IA", "3", "1", "3", "7", ""], ["IB", "4", "2", "7", "13", ""], ["IIA", "14", "8", "3", "25", ""], ["IIB", "39", "53", "20", "112", ""], ["III", "2", "1", "1", "4", ""], ["IV", "1", "1", "1", "3", ""], ["NA", "8", "3", "3", "14", ""], ["pT", "", "", "", "", ".060"], ["pT1", "3", "1", "4", "8", ""], ["pT2", "3", "9", "7", "19", ""], ["pT3", "56", "55", "23", "134", ""], ["pT4", "1", "1", "1", "3", ""], ["NA", "8", "3", "3", "14", ""], ["pN", "", "", "", "", ".034"], ["pN0", "20", "12", "12", "44", ""], ["pN1a", "41", "54", "19", "114", ""], ["pN1b", "1", "0", "2", "3", ""], ["NA", "9", "3", "5", "11", ""], ["Anatomic location", "", "", "", "", ".086"], ["Head of pancreas", "48", "58", "24", "130", ""], ["Body of pancreas", "6", "2", "3", "11", ""], ["Tail of pancreas", "7", "2", "4", "13", ""], ["Other location", "2", "4", "5", "11", ""], ["NA", "8", "3", "2", "13", ""]], "row_count": 31, "column_count": 6, "numeric_cells": 108, "header_rows": 1, "locator": "section[12]/table-wrap[1]#T1"}}, {"id": "asset:table:pmid:33832071:3", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:1de5db8fe729dae5ac26c116e8bdcb0b686ddd76099426186d6f4df91bf6b04f", "bytes": 866, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[15]/table-wrap[1]#T2", "version": null, "note": "Subgroup-specific altered canonical pathways and related molecules.", "structure": {"pmcid": "PMC8036077", "section_index": 15, "section_title": "Activated signaling pathways in three subtypes", "row_count": 13, "column_count": 4}, "table": {"label": "Table 2", "caption": "Subgroup-specific altered canonical pathways and related molecules.", "rows": [["Ingenuity canonical pathways", "-log (P)", "Ratio", "Molecules"], ["Subgroup 1"], ["ATM signaling", "3.06", "0.0625", "RAD51, CDC25C, TP73, CCNB2, CDK1"], ["FXR/RXR activation", "2.95", "0.0476", "G6PC2, TTR, SDC1, APOH, VTN, GC"], ["p53 signaling", "1.71", "0.036", "TP73, E2F1, BIRC5, KLB"], ["Subgroup 2"], ["Nicotine degradation II", "1.65", "0.0411", "UGT2A3, NADP, FMO4"], ["Notch signaling", "1.41", "0.0526", "NOTCH2, FURIN"], ["PTEN signaling", "1.11", "0.0248", "MAGI1, INSR, RAC3"], ["Subgroup 3"], ["FAK signaling", "1.24", "0.0303", "CAPN8, CAPN9, ACTC1"], ["ILK signaling", "1.01", "0.0204", "RHOV, MUC1, ITGB6, ACTC1"], ["PI3K signaling", ".978", "0.0234", "BLK, CD19, CR2"]], "row_count": 13, "column_count": 4, "numeric_cells": 25, "header_rows": 1, "locator": "section[15]/table-wrap[1]#T2"}}, {"id": "asset:table:pmid:33832071:4", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:4a731a7c10accb5d92d3119043c56fddfc9486712b36e3d5a571c6948f673a52", "bytes": 760, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[17]/table-wrap[1]#T3", "version": null, "note": "Uivariate and multivariate analysis of clinicopathologic factors and gene signatures using Cox regression analysis.", "structure": {"pmcid": "PMC8036077", "section_index": 17, "section_title": "Cox regression analysis and hazard ratio of each clinical variable and gene signatures", "row_count": 10, "column_count": 5}, "table": {"label": "Table 3", "caption": "Uivariate and multivariate analysis of clinicopathologic factors and gene signatures using Cox regression analysis.", "rows": [["Factors", "Exp (β)", "SE", "95.0% CI", "P"], ["Univariate analysis"], ["Gene signatures", "0.707", "0.150", "(0.526–0.948)", ".021∗"], ["Sex (male)", "0.894", "0.221", "(0.579–1.38)", ".61"], ["Node-positive", "2.031", "0.274", "(1.186–3.476)", ".0098∗"], ["Stage IV", "4.101", "1.007", "(0.569–29.53)", ".161"], ["T4", "1.613", "1.226", "(0.145–17.8)", ".697"], ["Multivariate analysis"], ["Gene signatures", "0.719", "1.39", "(0.523–0.98)", ".042∗"], ["Node-positive", "1.04", "0.8669", "(0.190–5.690)", ".963"]], "row_count": 10, "column_count": 5, "numeric_cells": 29, "header_rows": 1, "locator": "section[17]/table-wrap[1]#T3"}}], "gaps": ["asset:data:geo:GSE50827 not downloaded", "asset:data:geo:GSE50827 licence not read"]}, "analysis": {"state": "complete", "methods": [{"id": "method-1", "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": 1.0, "band": "verbatim", "quote": "Association of each subtype with overall survival was evaluated using Kaplan-Meier plots and log rank test."}}, {"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": "survival_analysis", "specific": "log_rank_test", "label": "Survival analysis", "dsl_operations": ["logrank_test"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["time_to_event_with_censoring"], "evidence": {"score": 0.8, "band": "high", "quote": "log rank"}}, {"id": "method-4", "family": "clustering", "specific": "hierarchical", "label": "Clustering", "dsl_operations": ["hierarchical_cluster"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["feature_matrix"], "evidence": {"score": 0.8, "band": "high", "quote": "hierarchical clustering"}}, {"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": "χ2"}}], "targets": [], "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": "complete", "tier": "R1", "blocking_axis": "none", "blocked_on": "nothing:replicable_now", "axes": {"method": {"tier": "R1", "expressible": true, "required_operations": ["survival_km"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: kaplan_meier."}, "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": ["GSE50827"], "resolved_accessions": ["GSE50827"], "statements": ["The datasets generated during and/or analyzed during the current study are publicly available."], "basis": "The paper names GSE50827 in Gene Expression Omnibus and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["survival_km"], "assets": ["source:pmid:33832071", "data:geo:GSE50827", "asset:table:pmid:33832071:1", "asset:table:pmid:33832071:2", "asset:table:pmid:33832071:3", "asset:table:pmid:33832071:4"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE50827"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-10-31T18:28:56Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 3, "usage": {"prompt_tokens": 17316, "completion_tokens": 1604, "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:33832071", "type": "paper", "label": "pmid:33832071"}, {"id": "source:pmid:33832071", "type": "manuscript", "label": "PMID 33832071 full text"}, {"id": "data:geo:GSE50827", "type": "dataset", "label": "GEO GSE50827"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:33832071", "type": "paper", "label": "pmid:33832071"}, {"id": "source:pmid:33832071", "type": "manuscript", "label": "PMID 33832071 full text"}, {"id": "data:geo:GSE50827", "type": "dataset", "label": "GEO GSE50827"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-33832071", "type": "extraction", "used": ["source:pmid:33832071"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE50827", "type": "accession_resolution", "used": ["data:geo:GSE50827"], "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:33832071", "parent_hash": "sha256:f0e1b197acb099a0a5c5f7b38b761a1626294ee2cb4eb2fb36d2b43a2b094dc2", "fork_of": null, "generation": 6}, "gaps": ["asset:data:geo:GSE50827 licence not read", "asset:data:geo:GSE50827 not downloaded", "execution.not_run", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "analysis", "definition_id": "survival_analysis", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["survival_km"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["Association of each subtype with overall survival was evaluated using Kaplan-Meier plots and log rank test."], "order_basis": "analysis_only", "id": "assay:1"}]}