A 15-Gene Immune, Stromal, and Proliferation Gene Signature that Significantly Associates with Poor Survival in Patients with Pancreatic Ductal Adenocarcinoma.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:32234757", "kind": "science-record", "revision": 4, "content_hash": "sha256:5c902b3b81cc0dc324f73aab33434957889fb57584e56371bd4796b902fc9a61", "created_at": "2026-11-01T17:33:30Z", "updated_at": "2026-11-01T22:44:42Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "A 15-Gene Immune, Stromal, and Proliferation Gene Signature that Significantly Associates with Poor Survival in Patients with Pancreatic Ductal Adenocarcinoma.", "doi": "10.1158/1078-0432.CCR-19-4044", "pmid": "32234757", "authors": ["Raju Kandimalla", "Hideo Tomihara", "Jasjit K Banwait", "Kensuke Yamamura", "Gagandeep Singh", "Hideo Baba", "Ajay Goel"], "journal": "Clinical cancer research : an official journal of the American Association for Cancer Research", "year": 2020, "abstract": "PURPOSE: Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease with dismal survival rates. Tumor microenvironment (TME), comprising of immune cells and cancer-associated fibroblasts, plays a key role in driving poor prognosis and resistance to chemotherapy. Herein, we aimed to identify a TME-associated, risk-stratification gene biomarker signature in PDAC.\nEXPERIMENTAL DESIGN: The initial biomarker discovery was performed in The Cancer Genome Atlas (TCGA, n = 163) transcriptomic data. This was followed by independent validation of the gene signature in the International Cancer Genome Consortium (ICGC, n = 95), E-MTAB-6134 (n = 288), and GSE71729 (n = 123) datasets for predicting overall survival (OS), and for its ability to detect poor molecular subtypes. Clinical validation and nomogram establishment was undertaken by performing multivariate Cox regression analysis.\nRESULTS: Our biomarker discovery effort identified a 15-gene immune, stromal, and proliferation (ISP) gene signature that significantly associated with poor OS [HR, 3.90; 95% confidence interval (CI), 2.36-6.41; P < 0.0001]. This signature also robustly predicted survival in three independent validation cohorts ICGC [HR, 2.63 (1.56-4.41); P < 0.0001], E-MTAB-6134 [HR, 1.53 (1.14-2.04); P = 0.004], and GSE71729 [HR, 2.33 (1.49-3.63); P < 0.0001]. Interestingly, the ISP signature also permitted identification of poor molecular PDAC subtypes with excellent accuracy in all four cohorts; TCGA (AUC = 0.94), ICGC (AUC = 0.91), E-MTAB-6134 (AUC = 0.80), and GSE71729 (AUC = 0.83). The ISP-derived high-risk patients exhibited significantly poor OS in a clinical validation cohort [n = 119; HR, 2.62 (1.50-4.56); P = 0.0004]. A nomogram was established which included the ISP, CA19-9, and T- and N-stage for eventual clinical translation.\nCONCLUSIONS: We report a novel gene signature for risk-stratification and robust identification of patients with PDAC with poor molecular subtypes.", "claims": [{"id": "claim-method", "statement": "To identify a clinically translatable immune, stromal and proliferative (ISP) gene signature, we performed Lasso penalized Cox regression analysis21 on these genes.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:32234757", "locator": "sections[6] \"Statistical analysis\" paragraph 2", "quote": "To identify a clinically translatable immune, stromal and proliferative (ISP) gene signature, we performed Lasso penalized Cox regression analysis21 on these genes."}], "state": "complete"}, {"id": "claim-data-access", "statement": "In the initial discovery phase, normalized RNA sequencing data from 163 PDAC patients was downloaded from the Broad GDAC Firehose (http://gdac.broadinstitute.org/) to identify a 15-gene ISP signature.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:32234757", "locator": "sections[3] \"Study design and patient cohorts\" paragraph 2", "quote": "In the initial discovery phase, normalized RNA sequencing data from 163 PDAC patients was downloaded from the Broad GDAC Firehose (http://gdac.broadinstitute.org/) to identify a 15-gene ISP signature."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The study identified a 15-gene immune, stromal and proliferation (ISP) signature that was significantly associated with poor overall survival in PDAC and robustly identified poor molecular subtypes across four cohorts.", "kind": "quantitative", "target": {"value": 95.0, "unit": "per cent", "tolerance": null, "source": "Our biomarker discovery effort identified a 15-gene immune, stromal and proliferation (ISP) gene signature that significantly associated with poor OS (HR: 3.90, 95% CI, 2.36–6.41, p<0.0001)."}, "evidence": [{"asset": "source:pmid:32234757", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "Our biomarker discovery effort identified a 15-gene immune, stromal and proliferation (ISP) gene signature that significantly associated with poor OS (HR: 3.90, 95% CI, 2.36–6.41, p<0.0001)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The study identified a 15-gene immune, stromal and proliferation (ISP) signature that was significantly associated with poor overall survival in PDAC and robustly identified poor molecular subtypes across four cohorts.", "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:32234757"], "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:E-MTAB-6134"], "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:E-MTAB-6134"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:32234757", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1158/1078-0432.CCR-19-4044", "sha256": 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