NOTCH4 Is a Novel Prognostic Marker that Correlates with Colorectal Cancer Progression and Prognosis.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:30026833", "kind": "science-record", "revision": 8, "content_hash": "sha256:a5668abbdb0ea5d43336fe26a551f6b23f3a4fb52ae49d161cb7a845f5d88d84", "created_at": "2026-11-01T15:40:35Z", "updated_at": "2026-11-01T21:59:57Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "NOTCH4 Is a Novel Prognostic Marker that Correlates with Colorectal Cancer Progression and Prognosis.", "doi": "10.7150/jca.26359", "pmid": "30026833", "authors": ["Guiyang Wu", "Zaiping Chen", "Jing Li", "Fubo Ye", "Guoping Chen", "Qinghao Fan", "Hao Dong", "Shichao Yuan", "Xiongwen Zhu"], "journal": "Journal of Cancer", "year": 2018, "abstract": "Notch family plays vital role in carcinogenesis and progression of various cancer, however, its clinical significance and prognostic value in colorectal cancer isn't fully investigated. In present study, we first investigated the NOTCH4 expression in The Cancer Genome Atlas (TCGA) (n=361) and GSE39582 (n=474) database and then validated with our own database (n=248). The transcriptional and protein levels of NOTCH4 were evaluated by RT-PCR and immunohistochemistry study, respectively. Univariate and multivariate survival analyses were performed to explore the relationship between various prognostic factors and survival outcomes. In the univariate analysis, NOTCH3 and NOTCH4 were significantly correlated with prognosis in TCGA and GSE39582 database, respectively (P<0.05). For NOTCH3 has been studied in CRC, we chosen NOTCH4 for further study. NOTCH4 mRNA was higher in liver metastases than their primary colorectal cancer or normal mucosa. Increased NOTCH4 levels significantly correlated with advanced N stage (P= 0.002), M stage (P= 0.002), lymphovascular invasion (P= 0.026), and CEA status (P= 0.030). Patients with high NOTCH4 expression had shorter 5-year disease-free survival (DFS) (HR 6.809; 95% CI 3.334-13.904; P< 0.001) and overall survival (OS) (HR 6.476; 95% CI 3.307-12.689; P<0.001) than those with low NOTCH4 expression. Multivariate survival analysis demonstrated that NOTCH4 was an independent prognostic biomarker for both DFS (HR 7.848; 95% CI 3.777-16.308; P<0.001) and OS (HR 5.323; 95% CI 2.668-10.623; P<0.001).Collectively, NOTCH4 may play critical role in colorectal cancer progression and could serve as a novel biomarker to predict survival after colectomy.", "claims": [{"id": "claim-method", "statement": "Univariate Cox proportional hazards regressions were applied to estimate the individual hazard ratio (HR) for the DFS and OS. The significant variables in the univariate analyses (P<0.05) were then put into the multivariate analysis.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:30026833", "locator": "sections[8] \"Statistical Analysis\" paragraph 2", "quote": "Univariate Cox proportional hazards regressions were applied to estimate the individual hazard ratio (HR) for the DFS and OS. The significant variables in the univariate analyses (P<0.05) were then put into the multivariate analysis."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The expression of Notch family in human CRC specimens were searched and analyzed in TCGA Illumina RNA-Seq datasets and GSE39582 raw microarray data. Gene-level expression data and their clinical characters of CRC samples were downloaded from TCGA database (https://genome-cancer.ucsc.edu/) and GSE39582 database (https://www.ncbi.nlm.nih.gov/geo/).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:30026833", "locator": "sections[3] \"Data selection in TCGA and GSE39582 cohort\" paragraphs 1-3", "quote": "The expression of Notch family in human CRC specimens were searched and analyzed in TCGA Illumina RNA-Seq datasets and GSE39582 raw microarray data. Gene-level expression data and their clinical characters of CRC samples were downloaded from TCGA database (https://genome-cancer.ucsc.edu/) and GSE39582 database (https://www.ncbi.nlm.nih.gov/geo/)."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Using univariate and multivariate survival analyses of NOTCH4 expression from TCGA (n=361), GSE39582 (n=474), and an external validation cohort (n=248), the study found that high NOTCH4 was an independent prognostic biomarker for shorter disease-free and overall survival.", "kind": "quantitative", "target": {"value": 95.0, "unit": "per cent", "tolerance": null, "source": "Patients with high NOTCH4 expression had shorter 5-year disease-free survival (DFS) (HR 6.809; 95% CI 3.334-13.904; P< 0.001) and overall survival (OS) (HR 6.476; 95% CI 3.307-12.689; P<0.001) than those with low NOTCH4 expression."}, "evidence": [{"asset": "source:pmid:30026833", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "In present study, we first investigated the NOTCH4 expression in The Cancer Genome Atlas (TCGA) (n=361) and GSE39582 (n=474) database and then validated with our own database (n=248)."}, {"asset": "source:pmid:30026833", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "Univariate and multivariate survival analyses were performed to explore the relationship between various prognostic factors and survival outcomes."}, {"asset": "source:pmid:30026833", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "Patients with high NOTCH4 expression had shorter 5-year disease-free survival (DFS) (HR 6.809; 95% CI 3.334-13.904; P< 0.001) and overall survival (OS) (HR 6.476; 95% CI 3.307-12.689; P<0.001) than those with low NOTCH4 expression."}, {"asset": "source:pmid:30026833", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "Multivariate survival analysis demonstrated that NOTCH4 was an independent prognostic biomarker for both DFS (HR 7.848; 95% CI 3.777-16.308; P<0.001) and OS (HR 5.323; 95% CI 2.668-10.623; P<0.001)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Using univariate and multivariate survival analyses of NOTCH4 expression from TCGA (n=361), GSE39582 (n=474), and an external validation cohort (n=248), the study found that high NOTCH4 was an independent prognostic biomarker for shorter disease-free and overall survival.", "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:30026833"], "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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