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pmid:34205690
A Comprehensive Bioinformatics Analysis of Notch Pathways in Bladder Cancer.
Chuan Zhang · Mandy Berndt-Paetz · Jochen Neuhaus
Cancers · 2021 doi:10.3390/cancers13123089
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Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:34205690", "kind": "science-record", "revision": 8, "content_hash": "sha256:13dba7aec528ad1411613ecfc83b7ca02c30ce7955d038643d99817c4422668a", "created_at": "2026-11-01T15:41:41Z", "updated_at": "2026-11-01T22:46:59Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "A Comprehensive Bioinformatics Analysis of Notch Pathways in Bladder Cancer.", "doi": "10.3390/cancers13123089", "pmid": "34205690", "authors": ["Chuan Zhang", "Mandy Berndt-Paetz", "Jochen Neuhaus"], "journal": "Cancers", "year": 2021, "abstract": "BACKGROUND: A hallmark of Notch signaling is its variable role in tumor biology, ranging from tumor-suppressive to oncogenic effects. Until now, the mechanisms and functions of Notch pathways in bladder cancer (BCa) are still unclear.\nMETHODS: We used publicly available data from the GTEx and TCGA-BLCA databases to explore the role of the canonical Notch pathways in BCa on the basis of the RNA expression levels of Notch receptors, ligands, and downstream genes. For statistical analyses of cancer and non-cancerous samples, we used R software packages and public databases/webservers.\nRESULTS: We found differential expression between control and BCa samples for all Notch receptors (NOTCH1, 2, 3, 4), the delta-like Notch ligands (DLL1, 3, 4), and the typical downstream gene hairy and enhancer of split 1 (HES1). NOTCH2/3 and DLL4 can significantly differentiate non-cancerous samples from cancers and were broadly altered in subgroups. High expression levels of NOTCH2/3 receptors correlated with worse overall survival (OS) and shorter disease-free survival (DFS). However, at long-term (>8 years) follow-up, NOTCH2 expression was associated with a better OS and DFS. Furthermore, the cases with the high levels of DLL4 were associated with worse OS but improved DFS. Pathway network analysis revealed that NOTCH2/3 in particular correlated with cell cycle, epithelial-mesenchymal transition (EMT), numbers of lymphocyte subtypes, and modulation of the immune system.\nCONCLUSIONS: NOTCH2/3 and DLL4 are potential drivers of Notch signaling in BCa, indicating that Notch and associated pathways play an essential role in the progression and prognosis of BCa through directly modulating immune cells or through interaction with cell cycle and EMT.", "claims": [{"id": "claim-method", "statement": "Univariate analysis was performed using ANOVA, t-test, Wilcoxon test, Tukey’s HSD, and permutation tests.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34205690", "locator": "sections[9] \"2.7. 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Furthermore, the other web servers provide easy access to publicly available cancer OMICS data (TCGA, GTEx, et al.) and allow users to identify biomarkers or to perform in silico validation of potential genes, including GEPIA, GeneMANIA, Oncomine, GSCALite, UALCAN, and TISIDB for analyzing RNA sequencing expression and other data projects via a standard processing pipeline, and following the guidelines in the Data Use Certification Agreement.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34205690", "locator": "sections[49] \"Data Availability Statement\" paragraph 2", "quote": "The data presented in this study are openly available in the Cancer Genome Atlas Program (TCGA), the Genotype-Tissue Expression (GTEx), and the Human Protein Atlas (HPA). Furthermore, the other web servers provide easy access to publicly available cancer OMICS data (TCGA, GTEx, et al.) and allow users to identify biomarkers or to perform in silico validation of potential genes, including GEPIA, GeneMANIA, Oncomine, GSCALite, UALCAN, and TISIDB for analyzing RNA sequencing expression and other data projects via a standard processing pipeline, and following the guidelines in the Data Use Certification Agreement."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "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:34205690"], "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. 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Gene Expression of Notch Pathway-Related Genes in BCa and Controls", "row_count": 29, "column_count": 13}, "table": {"label": "Table 2", "caption": "Statistically significant difference of expression levels of target genes in subgroups (1).", "rows": [["Target Genes", "BCa vs. Control", "p-Value", "Tumor Stage", "p-Value", "Lymph Nodal Metastasis", "p-Value", "HistologicalSubtypes", "p-Value", "Race", "p-Value", "Gender", "p-Value"], ["NOTCH1", "BCa (↓)", "p = 6.83 × 10−7", "", "", "C vs. N0 (↓)", "p = 7.35 × 10−3", "C vs. PT (↓)", "p = 1.52 × 10−3", "CAU vs. AFA (↑)", "p = 1.04 × 10−2", "", ""], ["", "", "", "", "C vs. N2 (↓)", "p = 3.67 × 10−4", "C vs. NPT (↓)", "p = 1.46 × 10−4", "", "", "", ""], ["NOTCH2", "BCa (↓)", "p = 9.46 × 10−9", "S2 vs. S3 (↑)", "p = 2.07 × 10−2", "C vs. N0 (↓)", "p = 1.00 × 10−7", "C vs. PT (↓)", "p = 6.00 × 10−5", "CAU vs. ASI (↓)", "p = 2.13 × 10−4", "", ""], ["", "", "S2 vs. S4 (↑)", "p = 2.81 × 10−2", "C vs. N1 (↓)", "p = 1.29 × 10−2", "C vs. NPT (↓)", "p < 0.000001", "AFA vs. ASI (↓)", "p = 1.00 × 10−7", "", ""], ["", "", "", "", "C vs. N2 (↓)", "p = 5.58 × 10−4", "PT vs. NPT (↑)", "p = 3.00 × 10−7", "", "", "", ""], ["NOTCH3", "BCa (↑)", "p = 1.98 × 10−4", "", "", "C vs. N0 (↑)", "p = 2.20 × 10−3", "C vs. PT (↑)", "p = 3.44 × 10−4", "", "", "", ""], ["", "", "", "", "C vs. N1 (↑)", "p = 6.35 × 10−4", "C vs. NPT (↑)", "p = 2.41 × 10−3", "", "", "", ""], ["", "", "", "", "C vs. N2 (↑)", "p = 1.45 × 10−2", "", "", "", "", "", ""], ["NOTCH4", "BCa (↓)", "p = 5.02 × 10−12", "", "", "C vs. N0 (↓)", "p < 0.000001", "C vs. PT (↓)", "p = 2.00 × 10−7", "AFA vs. ASI (↑)", "p = 2.59 × 10−3", "", ""], ["", "", "", "", "C vs. N1 (↓)", "p < 0.000001", "C vs. NPT (↓)", "p < 0.000001", "", "", "", ""], ["", "", "", "", "C vs. N2 (↓)", "p = 1.00 × 10−7", "PT vs. NPT (↓)", "p = 1.00 × 10−2", "", "", "", ""], ["", "", "", "", "C vs. N3 (↓)", "p = 7.17 × 10−4", "", "", "", "", "", ""], ["JAG1", "", "", "", "", "", "", "PT vs. NPT (↑)", "p = 6.77 × 10−4", "CAU vs. AFA (↑)", "p = 2.93 × 10−3", "", ""], ["", "", "", "", "", "", "", "", "AFA vs. ASI (↓)", "p = 1.47 × 10−2", "", ""], ["JAG2", "", "", "S2 vs. S4 (↓)", "p = 3.21 × 10−3", "C vs. N2 (↓)", "p = 1.06 × 10−2", "", "", "CAU vs. AFA (↑)", "p = 4.45 × 10−2", "Male vs. Female (↑)", "p = 3.20 × 10−4"], ["DLL1", "BCa (↓)", "p = 4.67 × 10−8", "", "", "C vs. N0 (↓)", "p = 1.84 × 10−4", "C vs. PT (↓)", "p = 1.00 × 10−7", "", "", "", ""], ["", "", "", "", "C vs. N1 (↓)", "p = 2.13 × 10−4", "C vs. NPT (↓)", "p = 1.85 × 10−5", "", "", "", ""], ["", "", "", "", "C vs. N2 (↓)", "p = 5.00 × 10−7", "PT vs. NPT (↑)", "p = 4.45 × 10−2", "", "", "", ""], ["", "", "", "", "C vs. N3 (↓)", "p = 1.08 × 10−2", "", "", "", "", "", ""], ["DLL3", "BCa (↑)", "p = 1.02 × 10−9", "", "", "C vs. N0 (↑)", "p = 3.00 × 10−7", "C vs. PT (↑)", "p = 9.51 × 10−5", "", "", "", ""], ["", "", "", "", "C vs. N1 (↑)", "p = 3.20 × 10−6", "C vs. NPT (↑)", "p < 0.000001", "", "", "", ""], ["", "", "", "", "C vs. N2 (↑)", "p = 3.80 × 10−6", "PT vs. NPT (↑)", "p = 2.26 × 10−2", "", "", "Male vs. Female (↑)", "p = 3.07 × 10−2"], ["", "", "", "", "C vs. N3 (↑)", "p = 2.36 × 10−3", "", "", "", "", "", ""], ["DLL4", "BCa (↓)", "p = 6.36 × 10−5", "", "", "C vs. N0 (↓)", "p = 7.29 × 10−3", "C vs. NPT (↓)", "p = 3.63 × 10−5", "CAU vs. ASI (↓)", "p = 1.55 × 10−02", "", ""], ["", "", "", "", "C vs. N1 (↓)", "p = 2.19 × 10−3", "PT vs. NPT (↓)", "p = 6.46 × 10−3", "AFA vs. ASI (↓)", "p = 2.22 × 10−02", "", ""], ["HES1", "BCa (↑)", "p = 2.61 × 10−5", "", "", "C vs. N0 (↑)", "p = 1.00 × 10−7", "C vs. PT (↑)", "p < 0.000001", "CAU vs. ASI (↓)", "p = 3.98 × 10−04", "", ""], ["", "", "", "", "C vs. N1 (↑)", "p = 3.63 × 10−3", "C vs. NPT (↑)", "p = 4.40 × 10−6", "", "", "", ""], ["", "", "", "", "C vs. N2 (↑)", "p = 2.25 × 10−5", "PT vs. NPT (↓)", "p = 5.05 × 10−3", "", "", "", ""]], "row_count": 29, "column_count": 13, "numeric_cells": 71, "header_rows": 1, "locator": "section[12]/table-wrap[1]#cancers-13-03089-t002"}}, {"id": "asset:table:pmid:34205690:3", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:ae4e2ed4d9a3066c1dbe7a91196ea65ff56065706c478a482a170af9fe104de7", "bytes": 3166, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[17]/table-wrap[1]#cancers-13-03089-t003", "version": null, "note": "Statistically significant differences of expression levels of target genes in subgroups (2).", "structure": {"pmcid": "PMC8235546", "section_index": 17, "section_title": "3.1.6. Gene Expression in Molecular Subtypes", "row_count": 33, "column_count": 9}, "table": {"label": "Table 3", "caption": "Statistically significant differences of expression levels of target genes in subgroups (2).", "rows": [["Target Genes", "Molecular Subtypes", "TP53 Mutation Status"], ["", "C-TCGA vs. Subtypes", "p-Value", "BST vs. LT/LIT", "p-Value", "C-TCGA vs. TP53M/TP53WT", "p-Value", "TP53M vs. TP53WT", "p-Value"], ["NOTCH1", "LT (↓)", "p = 8.20 × 10−3", "LT (↓)", "p = 3.31 × 10−2", "TP53M (↓)", "p = 6.20 × 10−3", "TP53WT (↑)", "p = 3.91 × 10−7"], ["", "", "", "LT (↓)", "p = 6.16 × 10−4", "", "", "", ""], ["NOTCH2", "LT (↓)", "p = 1.50 × 10−3", "LT (↓)", "p = 1.14 × 10−3", "TP53M (↓)", "p = 3.46 × 10−2", "TP53WT (↓)", "p = 4.34 × 10−2"], ["", "LIT (↓)", "p = 3.68 × 10−2", "", "", "TP53WT (↓)", "p = 1.17 × 10−2", "", ""], ["", "LPT (↓)", "p = 5.44 × 10−3", "", "", "", "", "", ""], ["NOTCH3", "BST (↑)", "p = 5.69 × 10−5", "LIT (↑)", "p = 4.05 × 10−2", "TP53M (↑)", "p = 5.83 × 10−4", "", ""], ["", "LT (↑)", "p = 1.26 × 10−3", "", "", "TP53WT (↑)", "p = 2.22 × 10−5", "", ""], ["", "LIT (↑)", "p = 1.06 × 10−2", "", "", "", "", "", ""], ["", "LPT (↑)", "p = 8.22 × 10−5", "", "", "", "", "", ""], ["NOTCH4", "BST (↓)", "p = 1.47 × 10−2", "LIT (↑)", "p = 9.78 × 10−3", "TP53M (↓)", "p = 3.02 × 10−2", "TP53WT (↑)", "p = 4.62 × 10−3"], ["JAG1", "BST (↑)", "p = 1.10 × 10−6", "LT (↓)", "p = 9.77 × 10−5", "TP53M (↑)", "p = 3.95 × 10−2", "", ""], ["", "", "", "LIT (↓)", "p = 1.13 × 10−7", "", "", "", ""], ["JAG2", "NET (↑)", "p = 2.09 × 10−2", "LT (↓)", "p = 5.25 × 10−12", "TP53M (↑)", "p = 1.32 × 10−3", "", ""], ["", "BST (↑)", "p = 4.76 × 10−8", "LIT (↓)", "p = 5.87 × 10−9", "TP53WT (↑)", "p = 3.98 × 10−4", "", ""], ["", "LPT (↑)", "p = 3.99 × 10−2", "", "", "", "", "", ""], ["DLL1", "LT (↓)", "p = 3.06 × 10−3", "LT (↓)", "p = 1.44 × 10−4", "", "", "TP53WT (↓)", "p = 2.86 × 10−2"], ["", "LIT (↓)", "p = 5.54 × 10−3", "LIT (↓)", "p = 7.74 × 10−5", "", "", "", ""], ["", "LPT (↓)", "p = 1.31 × 10−3", "", "", "", "", "", ""], ["DLL3", "BST (↑)", "p = 3.48 × 10−7", "LIT (↓)", "p = 1.96 × 10−3", "TP53M (↑)", "p = 1.00 × 10−2", "", ""], ["", "LT (↑)", "p = 4.68 × 10−2", "", "", "TP53WT (↑)", "p = 1.75 × 10−6", "", ""], ["", "LIT (↑)", "p = 9.80 × 10−3", "", "", "", "", "", ""], ["", "LPT (↑)", "p = 5.16 × 10−3", "", "", "", "", "", ""], ["DLL4", "", "", "LT (↑)", "p = 1.77 × 10−2", "", "", "TP53WT (↑)", "p = 4.02 × 10−3"], ["", "", "", "LIT (↑)", "p = 4.46 × 10−3", "", "", "", ""], ["HES1", "LT (↑)", "p = 3.51 × 10−3", "LT (↑)", "p = 3.97 × 10−5", "TP53WT (↑)", "p = 2.30 × 10−2", "TP53WT (↑)", "p = 2.11 × 10−2"], ["", "LIT (↑)", "p = 4.79 × 10−2", "LIT (↑)", "p = 2.18 × 10−3", "", "", "", ""], ["", "LPT (↑)", "p = 3.14 × 10−6", "", "", "", "", "", ""], ["HEY1", "NET (↑)", "p = 4.46 × 10−2", "LT (↑)", "p = 2.20 × 10−2", "TP53M (↑)", "p = 1.16 × 10−3", "", ""], ["", "BST (↑)", "p = 5.74 × 10−3", "", "", "TP53WT (↑)", "p = 1.63 × 10−6", "", ""], ["", "LT (↑)", "p = 1.68 × 10−3", "", "", "", "", "", ""], ["", "LIT (↑)", "p = 1.50 × 10−2", "", "", "", "", "", ""]], "row_count": 33, "column_count": 9, "numeric_cells": 87, "header_rows": 2, "locator": "section[17]/table-wrap[1]#cancers-13-03089-t003"}}, {"id": "asset:table:pmid:34205690:4", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:7167844ffc85754e135b8e3fdc860b07734456a444699116eb3bde94a28ba1c2", "bytes": 1038, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[24]/table-wrap[1]#cancers-13-03089-t004", "version": null, "note": "Risk assessment of Notch components on OS.", "structure": {"pmcid": "PMC8235546", "section_index": 24, "section_title": "3.3.1. Dependency of Overall Survival (OS) on the Expression Levels of Target Genes", "row_count": 13, "column_count": 8}, "table": {"label": "Table 4", "caption": "Risk assessment of Notch components on OS.", "rows": [["", "Univariate Test", "", "", "Multivariate Test", ""], ["Gene", "HR", "CI95", "p-Value", "Gene", "HR", "CI95", "p-Value"], ["NOTCH1", "1.21", "0.9–1.63", "0.208", "", "", "", ""], ["NOTCH2", "1.44", "1.06–1.96", "0.018 *", "NOTCH2", "1.27", "0.92–1.76", "0.151"], ["NOTCH3", "1.6", "1.2–2.15", "0.002 **", "NOTCH3", "1.65", "1.2–2.25", "0.002 **"], ["NOTCH4", "1.35", "0.85–2.15", "0.204", "", "", "", ""], ["JAG1", "4.26", "1.98–9.18", "0", "JAG1", "3.69", "1.67–8.15", "0.001 **"], ["JAG2", "1.25", "0.88–1.77", "0.221", "", "", "", ""], ["DLL1", "1.47", "0.87–2.5", "0.154", "", "", "", ""], ["DLL3", "0.89", "0.64–1.24", "0.483", "", "", "", ""], ["DLL4", "1.53", "1.11–2.1", "0.009 **", "DLL4", "1.54", "1.11–2.14", "0.009 **"], ["HES1", "0.57", "0.41–0.8", "0.001 **", "HES1", "0.56", "0.39–0.81", "0.002 **"], ["HEY1", "2.26", "1–5.11", "0.045 *", "HEY1", "1.63", "0.7–3.77", "0.255"]], "row_count": 13, "column_count": 8, "numeric_cells": 53, "header_rows": 2, "locator": "section[24]/table-wrap[1]#cancers-13-03089-t004"}}, {"id": "asset:table:pmid:34205690:5", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:58945db4b1ae3144c43fa25b29629ff7ce92d75478ba05fe02e5a63c40d38e25", "bytes": 1063, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[25]/table-wrap[1]#cancers-13-03089-t005", "version": null, "note": "Risk assessment of Notch components on DFS.", "structure": {"pmcid": "PMC8235546", "section_index": 25, "section_title": "3.3.2. Dependency of Disease-Free Survival (DFS) on the Expression Levels of Target Genes", "row_count": 13, "column_count": 8}, "table": {"label": "Table 5", "caption": "Risk assessment of Notch components on DFS.", "rows": [["", "Univariate Test", "", "", "Multivariate Test", ""], ["Gene", "HR", "CI95", "p-Value", "Gene", "HR", "CI95", "p-Value"], ["NOTCH1", "1.18", "0.85–1.65", "0.322", "", "", "", ""], ["NOTCH2", "1.53", "1.09–2.16", "0.014 *", "NOTCH2", "1.3", "0.91–1.85", "0.152"], ["NOTCH3", "1.46", "1.05–2.04", "0.026 *", "NOTCH3", "1.52", "1.08–2.15", "0.016 *"], ["NOTCH4", "0.88", "0.63–1.23", "0.447", "", "", "", ""], ["JAG1", "1.9", "1.02–3.52", "0.042 *", "JAG1", "1.42", "0.75–2.68", "0.28"], ["JAG2", "1.66", "1.07–2.58", "0.023 *", "JAG2", "1.63", "1.05–2.55", "0.03 *"], ["DLL1", "1.12", "0.81–1.56", "0.494", "", "", "", ""], ["DLL3", "1.19", "0.85–1.67", "0.3", "", "", "", ""], ["DLL4", "0.65", "0.44–0.95", "0.028 *", "DLL4", "0.68", "0.46–1.01", "0.056"], ["HES1", "0.56", "0.39–0.82", "0.003 **", "HES1", "0.59", "0.4–0.88", "0.01 *"], ["HEY1", "1.97", "1–3.87", "0.046 *", "HEY1", "1.67", "0.84–3.34", "0.146"]], "row_count": 13, "column_count": 8, "numeric_cells": 56, "header_rows": 2, "locator": "section[25]/table-wrap[1]#cancers-13-03089-t005"}}, {"id": "asset:table:pmid:34205690:6", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:c559fbbecd36873c68ce772b0b37527ecef87df6a0924e26ed5eb4a16b9f7842", "bytes": 2461, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[36]/table-wrap[1]#cancers-13-03089-t006", "version": null, "note": "The dual role of Notch receptors and ligands in BCa.", "structure": {"pmcid": "PMC8235546", "section_index": 36, "section_title": "4.1. NOTCH2/3 and DLL4 Are Potential Drivers of Notch Signaling in BCa", "row_count": 19, "column_count": 3}, "table": {"label": "Table 6", "caption": "The dual role of Notch receptors and ligands in BCa.", "rows": [["Name", "Role in BCa", "Description"], ["NOTCH1", "Suppression *(↓)", "Activated NOTCH1 suppressed BCa in vitro and in vivo by reducing ERK1 and ERK2(ERK1/2) [8]. Suppression of NOTCH1 may be advantageous for tumor progression [6]."], ["Oncogene (↑)", "NOTCH1 knockdown led to cancer cell growth and significantly inhibited growth and proliferation [72]."], ["NOTCH2", "Suppression *(↓)", "NOTCH2 was significantly downregulated in BCa [6,8]. Inactivation of NOTCH2 favors the process of EMT and promotes BCa progression [7]."], ["Oncogene (↑)", "High rate of NOTCH2 copy number gain and over-expression in BCa, and the activation of NOTCH2 promotes metastasis, resulting in poor survival [5]."], ["NOTCH3", "Suppression (↓)", "Deletion of the intracellular domain of NOTCH3 leads to negative function in BCa, i.e., turning it into potential tumor-suppressive gene [8]."], ["Oncogene*(↑)", "Significantly upregulated NOTCH3 enhanced the BCa growth and chemoresistance in urothelial carcinoma with worse survival [9]."], ["NOTCH4", "Suppression * (↓)", "NOTCH4 was significantly downregulated in BCa, especially in the T1 stage of bladder tumor. However, in patients diagnosed with muscle-invasive bladder tumor (MIBC), high NOTCH4 expression correlated with poor survival and more vascular invasion [73]."], ["Oncogene", "NA"], ["JAG1", "Suppression (↓)", "JAG1 significantly decreased in BCa and was associated with poor prognosis [74]."], ["Oncogene (↑)", "miR-489 directly suppressed JAG1 expression, inhibiting the proliferation and invasion of human bladder cancer cells [75]."], ["JAG2", "Suppression", "NA"], ["Oncogene (↑)", "JAG2 was overexpressed in BCa and was significantly associated with the metastasis and recurrence [76]."], ["DLL1", "Suppression *(↓)", "DLL1 was significantly decreased in BCa. Supposed to be a suppressive gene [6]."], ["Oncogene", "NA"], ["DLL3", "Suppression", "NA"], ["Oncogene * (↑)", "DLL3 was significantly upregulated in small cell components correlated with worse clinical outcomes in small cell bladder cancer (SCBC) [77]."], ["DLL4", "Suppression", "NA"], ["Oncogene (↑)", "DLL4 was significantly upregulated in BCa, and the expression of DLL4 was found to be associated with vascular differentiation in BCa [78]."]], "row_count": 19, "column_count": 3, "numeric_cells": 13, "header_rows": 1, "locator": "section[36]/table-wrap[1]#cancers-13-03089-t006"}}, {"id": "asset:table:pmid:34205690:7", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:c111a0a22795f380172ebf4ada6439c441aa0e9f3fc38cb11fcff65602905e42", "bytes": 1940, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[43]/table-wrap[1]#array1", "version": null, "note": 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(iii) IHC image credit: Human Protein Atlas (https://w", "as.org/, accessed on 13 December 2020) [62]; IHC staining of NOTCH3 (A3) and DLL4 (B3) in nor", "get genes is summarized in Figure S9. 3.5.3. IHC of Notch-Related Proteins in Normal Bladder"], "order_basis": "paper_text_order:7902", "id": "assay:1"}, {"role": "analysis", "definition_id": "group_comparison", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["Univariate analysis was performed using ANOVA, t-test, Wilcoxon test, Tukey’s HSD, and permutation tests."], "order_basis": "consumes_earlier_output", "id": "assay:2"}]}