Collagen stiffness promoted non-muscle-invasive bladder cancer progression to muscle-invasive bladder cancer.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:31123405", "kind": "science-record", "revision": 8, "content_hash": "sha256:228d9c68f67ffb5f679b6144b940cc90b15e844841f8553f20e639eee4c59cc6", "created_at": "2026-11-01T15:40:45Z", "updated_at": "2026-11-01T22:00:34Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Collagen stiffness promoted non-muscle-invasive bladder cancer progression to muscle-invasive bladder cancer.", "doi": "10.2147/OTT.S194568", "pmid": "31123405", "authors": ["Huier Zhu", "Hui Chen", "Jizhong Wang", "Ling Zhou", "Shaoyan Liu"], "journal": "OncoTargets and therapy", "year": 2019, "abstract": "Purpose: Bladder cancer (BCa) is generally considered one of the most prevalent deadly diseases worldwide. Patients suffering from muscle-invasive bladder cancer (MIBC) possess dismal prognoses, while those with non-muscle-invasive bladder cancer (NMIBC) generally have a favorable outcome after local treatment. However, some NMIBCs relapse and progress to MIBC, with an unclarified mechanism. Hence, insight into the genetic drivers of BCa progression has tremendous potential benefits for precision therapeutics, risk stratification, and molecular diagnosis. Methods: In this study, three cohorts profile datasets (GSE13507, GSE32584, and GSE89) consisting of NMIBC and MIBC samples were integrated to address the differently expressed genes (DEGs). Subsequently, the protein-protein interaction (PPI) network and pathway enrichment analysis of DGEs were performed. Results: Six collagen members (COL1A1, COL1A2, COL5A2, COL6A1, COL6A2, and COL6A3) were up-regulated and gathered in the ECM-receptor interaction signal pathway identified by KEGG pathway analysis and GSEA. Evidence derived from the Oncomine and TCGA databases indicated that the 6 collagen genes promote the progression of BCa and are negatively associated with patient prognosis. Moreover, taking COL1A1 as a further research object, the results showed that COL1A1 was up-regulated in MIBC and its knockdown significantly inhibited the proliferation, migration, and invasion of 5637 and T24 cells by inhibiting epithelial-mesenchymal transition (EMT) process and the TGF-β signaling pathway. Conclusion: With integrated bioinformatic analysis and cell experiments, we showed that 6 collagen family members are high progression risk factors and that they can be used as independent effective diagnostic and prognostic biomarkers for BCa.", "claims": [{"id": "claim-method", "statement": "The survival curve between the groups was described by the Kaplan-Meier plot and was evaluated using the log-rank test.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:31123405", "locator": "sections[15] \"Statistics\" paragraph 2", "quote": "The survival curve between the groups was described by the Kaplan-Meier plot and was evaluated using the log-rank test."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The array data for GSE13507 consisted of 103 NMIBC tissue samples and 61 MIBC tissue samples.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:31123405", "locator": "sections[3] \"Microarray data information and degs identification\" paragraph 2", "quote": "The array data for GSE13507 consisted of 103 NMIBC tissue samples and 61 MIBC tissue samples."}], "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:31123405"], "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:GSE13507"], "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:GSE13507"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:31123405", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.2147/OTT.S194568", "sha256": 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pathway may promote BCa progression", "row_count": 3, "column_count": 2}, "table": {"label": "Table 1", "caption": "Forty-five DEGs were identified from GSE89, GSE13507, and GSE32548 expression profile datasets", "rows": [["DEGs", "Genes Name"], ["Up-regulated", "ACTA2, ACTN1, AIF1, C1QB, CD14, CDC20, COL1A1, COL1A2, COL5A2, COL6A1, COL6A2, COL6A3, CRIP1, CTGF, DPYSL2, LGALS1, MGP, MMP9, MT2A, PDGFRB, PLEK, RBP1, RGS1, SLC2A3, SPP1, TAGLN, TGFBI, THY1, TPM2, VIM"], ["Down-regulated", "CTSE, CYP2J2, CYP4B1, DHRS2, FABP6, FOXA1, GPX2, HMGCS2, HSD17B2, ID3, PTK6,SLC14A1,SMAD6, SORL1, SPINK1"]], "row_count": 3, "column_count": 2, "numeric_cells": 2, "header_rows": 1, "locator": "section[17]/table-wrap[1]#T0001"}}, {"id": "asset:table:pmid:31123405:2", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:e65d82f5afd55a8a66794d8aa61d719ab9bfa016f762cdd6c1ab0a799d880ff4", "bytes": 2071, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[17]/table-wrap[2]#T0002", "version": null, "note": "The significant GO terms analysis of DEGs", "structure": {"pmcid": "PMC6511250", "section_index": 17, "section_title": "The ECM-receptor interaction signal pathway may promote BCa progression", "row_count": 28, "column_count": 4}, "table": {"label": "Table 2", "caption": "The significant GO terms analysis of DEGs", "rows": [["Category", "Term", "Count", "P-value"], ["Up-regulated (Top20)", "", "", ""], ["GOTERM_CC_FAT", "GO:0005578~proteinaceous extracellular matrix", "11", "1.97E-10"], ["GOTERM_CC_FAT", "GO:0031012~extracellular matrix", "11", "4.11E-10"], ["GOTERM_CC_FAT", "GO:0044421~extracellular region part", "13", "6.26E-08"], ["GOTERM_CC_FAT", "GO:0005581~collagen", "5", "5.72E-07"], ["GOTERM_CC_FAT", "GO:0005576~extracellular region", "16", "5.73E-07"], ["GOTERM_MF_FAT", "GO:0048407~platelet-derived growth factor binding", "4", "1.63E-06"], ["GOTERM_BP_FAT", "GO:0030198~extracellular matrix organization", "6", "2.08E-06"], ["GOTERM_BP_FAT", "GO:0001501~skeletal system development", "8", "2.94E-06"], ["GOTERM_BP_FAT", "GO:0007155~cell adhesion", "10", "7.17E-06"], ["GOTERM_BP_FAT", "GO:0022610~biological adhesion", "10", "7.26E-06"], ["GOTERM_BP_FAT", "GO:0043062~extracellular structure organization", "6", "1.88E-05"], ["GOTERM_MF_FAT", "GO:0005201~extracellular matrix structural constituent", "5", "3.76E-05"], ["GOTERM_CC_FAT", "GO:0044420~extracellular matrix part", "5", "7.27E-05"], ["GOTERM_MF_FAT", "GO:0019838~growth factor binding", "5", "8.21E-05"], ["GOTERM_BP_FAT", "GO:0001503~ossification", "5", "8.67E-05"], ["GOTERM_BP_FAT", "GO:0060348~bone development", "5", "1.13E-04"], ["GOTERM_CC_FAT", "GO:0005583~fibrillar collagen", "3", "2.40E-04"], ["GOTERM_CC_FAT", "GO:0005615~extracellular space", "8", "2.53E-04"], ["GOTERM_MF_FAT", "GO:0005178~integrin binding", "4", "2.99E-04"], ["GOTERM_BP_FAT", "GO:0048705~skeletal system morphogenesis", "4", "1.56E-03"], ["Down-regulated", "", "", ""], ["GOTERM_BP_FAT", "GO:0008202~steroid metabolic process", "5", "3.10474E-05"], ["GOTERM_BP_FAT", "GO:0055114~oxidation reduction", "5", "0.002505005"], ["GOTERM_MF_FAT", "GO:0009055~electron carrier activity", "3", "0.022942517"], ["GOTERM_MF_FAT", "GO:0070330~aromatase activity", "2", "0.026636667"], ["GOTERM_MF_FAT", "GO:0016712~oxidoreductase activity", "2", "0.031884301"]], "row_count": 28, "column_count": 4, "numeric_cells": 76, "header_rows": 1, "locator": "section[17]/table-wrap[2]#T0002"}}, {"id": "asset:table:pmid:31123405:3", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:cb603e3b5329aa325644da1570a88539ff9e71e34d2715f519719be13b575021", "bytes": 735, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[17]/table-wrap[3]#T0003", "version": null, "note": "The significant signaling pathway enrichment analysis of DEGs functions", "structure": {"pmcid": "PMC6511250", "section_index": 17, "section_title": "The ECM-receptor interaction signal pathway may promote BCa progression", "row_count": 6, "column_count": 4}, "table": {"label": "Table 3", "caption": "The significant signaling pathway enrichment analysis of DEGs functions", "rows": [["Pathway Name", "Gene Count", "p-value", "Genes"], ["Focal adhesion", "9", "8.9E-07", "COL6A3,COL6A2, COL1A2, COL6A1, ACTN1, PDGFRB, COL1A1, COL5A2, SPP1"], ["PI3K-Akt signaling pathway", "8", "2.6E-04", "COL6A3,COL6A2,COL1A2,COL6A1,PDGFRB, COL1A1, COL5A2, SPP1"], ["ECM-receptor interaction", "7", "8.9E-07", "COL6A3,COL6A2,COL1A2,COL6A1, COL1A1, COL5A2, SPP1"], ["Protein digestion and absorption", "6", "1.7E-05", "COL6A3,COL6A2,COL1A2,COL6A1, COL1A1, COL5A2"], ["Amoebiasis", "5", "7.5E-04", "COL1A2, ACTN1, COL1A1, COL5A2, CD14"]], "row_count": 6, "column_count": 4, "numeric_cells": 11, 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The followi", "to 5637 and T24 cells for 48h. The following siRNA sequences were used: COL1A1#NC, sense: 5‘-AC"], "order_basis": "paper_text_order:1434", "id": "assay:1"}, {"role": "data_generation", "definition_id": "ihc", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["Materials and methods Tissue samples and immunohistochemistry (IHC) staining In this study, a total of 30", "ods Tissue samples and immunohistochemistry (IHC) staining In this study, a total of 30 tisuu"], "order_basis": "paper_text_order:1918", "id": "assay:2"}, {"role": "data_generation", "definition_id": "cell_culture", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.77, "evidence": ["Shanghai, China. 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