Pathway-based gene signatures predicting clinical outcome of lung adenocarcinoma.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:26042604", "kind": "science-record", "revision": 7, "content_hash": "sha256:b470ae4e086e3e26b1f7a59642e5b488b16cd943586551981d6713c2110de372", "created_at": "2026-11-01T15:40:09Z", "updated_at": "2026-11-01T21:20:00Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Pathway-based gene signatures predicting clinical outcome of lung adenocarcinoma.", "doi": "10.1038/srep10979", "pmid": "26042604", "authors": ["Ya-Hsuan Chang", "Chung-Ming Chen", "Hsuan-Yu Chen", "Pan-Chyr Yang"], "journal": "Scientific reports", "year": 2015, "abstract": "Lung adenocarcinoma is often diagnosed at an advanced stage with poor prognosis. Patients with different clinical outcomes may have similar clinico-pathological characteristics. The results of previous studies for biomarkers for lung adenocarcinoma have generally been inconsistent and limited in clinical application. In this study, we used inverse-variance weighting to combine the hazard ratios for the four datasets and performed pathway analysis to identify prognosis-associated gene signatures. A total of 2,418 genes were found to be significantly associated with overall survival. Of these, a 21-gene signature in the HMGB1/RAGE signalling pathway and a 31-gene signature in the clathrin-coated vesicle cycle pathway were significantly associated with prognosis of lung adenocarcinoma across all four datasets (all p-values < 0.05, log-rank test). We combined the scores for the three pathways to derive a combined pathway-based risk (CPBR) score. Three pathway-based signatures and CPBR score also had more predictive power than single genes. Finally, the CPBR score was validated in two independent cohorts (GSE14814 and GSE13213 in the GEO database) and had significant adjusted hazard ratios 2.72 (p-value < 0.0001) and 1.71 (p-value < 0.0001), respectively. These results could provide a more complete picture of the lung cancer pathogenesis.", "claims": [{"id": "claim-method", "statement": "In order to determine whether genes were significantly associated with overall survival, multivariate Cox proportional hazards regression using the clinical covariates of age, sex and stage was performed on each of the 4 datasets. Each gene in a given dataset was assigned a hazard ratio (HR), and the corresponding p value was estimated by Cox regression analysis, giving 4 HR and 4 p values for each gene, then the inverse-variance weighting method was used to combine the HRs from the four datasets38. The gene expression and clinical data for these 4 groups were obtained from https://array.nci.nih.gov/caarray/project/details.action? project.id= 182.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:26042604", "locator": "sections[17] \"Identification of genes showing statistically significant differential expression using multivariate Cox proportional hazards regression\" paragraph 2", "quote": "In order to determine whether genes were significantly associated with overall survival, multivariate Cox proportional hazards regression using the clinical covariates of age, sex and stage was performed on each of the 4 datasets."}, {"asset": "source:pmid:26042604", "locator": "sections[17] \"Identification of genes showing statistically significant differential expression using multivariate Cox proportional hazards regression\" paragraph 2", "quote": "Each gene in a given dataset was assigned a hazard ratio (HR), and the corresponding p value was estimated by Cox regression analysis, giving 4 HR and 4 p values for each gene, then the inverse-variance weighting method was used to combine the HRs from the four datasets38."}, {"asset": "source:pmid:26042604", "locator": "sections[15] \"Study population and gene expression data\" paragraph 2", "quote": "The gene expression and clinical data for these 4 groups were obtained from https://array.nci.nih.gov/caarray/project/details.action? project.id= 182."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The gene expression and clinical data for these 4 groups were obtained from https://array.nci.nih.gov/caarray/project/details.action? project.id= 182.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:26042604", "locator": "sections[15] \"Study population and gene expression data\" paragraph 2", "quote": "The gene expression and clinical data for these 4 groups were obtained from https://array.nci.nih.gov/caarray/project/details.action? project.id= 182."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Using inverse-variance weighting to combine Cox-regression hazard ratios from four National Cancer Institute caArray lung adenocarcinoma datasets, the study identified three prognosis-associated pathway signatures and combined them into a CPBR score that was validated in two independent cohorts.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:26042604", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "In this study, we used inverse-variance weighting to combine the hazard ratios for the four datasets and performed pathway analysis to identify prognosis-associated gene signatures."}, {"asset": "source:pmid:26042604", "locator": "sections[6] \"Identification of genes with a significant hazard ratio (HR) and their associated pathways\" paragraph 2", "quote": "The study population consisted of 443 patients with lung adenocarcinoma from the University of Michigan Cancer Center (UM) (n = 178), the Moffitt Cancer Center (HLM) (n = 79), the Memorial Sloan-Kettering Cancer Center (MSK) (n = 104) and the Dana-Farber Cancer Institute (CAN/DF) (n = 82)7."}, {"asset": "source:pmid:26042604", "locator": "sections[17] \"Identification of genes showing statistically significant differential expression using multivariate Cox proportional hazards regression\" paragraph 2", "quote": "In order to determine whether genes were significantly associated with overall survival, multivariate Cox proportional hazards regression using the clinical covariates of age, sex and stage was performed on each of the 4 datasets."}, {"asset": "source:pmid:26042604", "locator": "sections[17] \"Identification of genes showing statistically significant differential expression using multivariate Cox proportional hazards regression\" paragraph 2", "quote": "Each gene in a given dataset was assigned a hazard ratio (HR), and the corresponding p value was estimated by Cox regression analysis, giving 4 HR and 4 p values for each gene, then the inverse-variance weighting method was used to combine the HRs from the four datasets38."}, {"asset": "source:pmid:26042604", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "We combined the scores for the three pathways to derive a combined pathway-based risk (CPBR) score."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Using inverse-variance weighting to combine Cox-regression hazard ratios from four National Cancer Institute caArray lung adenocarcinoma datasets, the study identified three prognosis-associated pathway signatures and combined them into a CPBR score that was validated in two independent 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:26042604"], "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. 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