Prognostic Impact of Thrombospodin-2 (THBS2) Overexpression on Patients with Urothelial Carcinomas of Upper Urinary Tracts and Bladders.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:27471570", "kind": "science-record", "revision": 9, "content_hash": "sha256:46c4df662515959f5461d6431a51c5132f1149882b78ed2347b60ac0a8470c14", "created_at": "2026-11-01T15:40:19Z", "updated_at": "2026-11-01T22:42:44Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Prognostic Impact of Thrombospodin-2 (THBS2) Overexpression on Patients with Urothelial Carcinomas of Upper Urinary Tracts and Bladders.", "doi": "10.7150/jca.15696", "pmid": "27471570", "authors": ["I-Wei Chang", "Chien-Feng Li", "Victor Chia-Hsiang Lin", "Hong-Lin He", "Per-In Liang", "Wen-Jeng Wu", "Ching-Chia Li", "Chun-Nung Huang"], "journal": "Journal of Cancer", "year": 2016, "abstract": "PURPOSE: Urothelial carcinoma (UC) is a type of tumor, especially of the urinary bladder, that affects people worldwide. Clarification of its detailed tumor biology and discovery of potential targets for developing treatment strategies are imperative because of frequent recurrences and poor prognosis of advanced UCs. By data mining a published dataset of UC of bladder (UCB) transcriptome (GSE31684) from Gene Expression Omnibus, National Center of Biotechnology Information (GEO, NCBI), we identified that THBS2 was the most significantly upregulated gene among those related to structural molecule activity (GO:0005198). Therefore, we evaluated the clinical significance and prognostic impact of thrombospondin-2 (THBS2) protein, A.K.A. TSP2, which encoded by THBS2 gene.\nMATERIALS AND METHODS: THBS2 immunostaining was performed in 340 UCs of upper urinary tract (UC-UUTs) and 295 UCBs; subsequently, both groups were dichotomized into high- and low-expression subgroups. Moreover, statistical analyses were performed to correlate the association between THBS2 expression and clinicopathological parameters with two survival indexes: disease-specific survival (DSS) and metastasis-free survival (MeFS).\nRESULTS: High THBS2 immunoexpression was significantly associated with advanced primary tumor status, nodal metastasis, and vascular invasion in both UC-UUT and UCB groups (all P ≤ .001). In addition, THBS2 overexpression was linked to adverse DSS and MeFS in univariate analyses and served as an independent prognosticator indicating poor outcomes in both groups in multivariate analyses.\nCONCLUSION: THBS2 may play a crucial role in UC progression and may be a novel prognostic marker. Additional investigations to elucidate the molecular pathway are necessary for developing potential THBS2-targeted therapies for UCs.", "claims": [{"id": "claim-method", "statement": "We applied Pearson's chi-squared test to compare the association between THBS2 expression and miscellaneous critical categorical clinical and pathological parameters and Mann-Whitney U test for numerical parameters. For univariate survival analyses, Kaplan-Meier survival curves, with comparison by using log-rank test, were utilized. Parameters demonstrating P < .05 in univariate analyses were included in multivariate tests by using Cox proportional hazards regression.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:27471570", "locator": "sections[6] \"Statistical Analyses\" paragraph 2", "quote": "We applied Pearson's chi-squared test to compare the association between THBS2 expression and miscellaneous critical categorical clinical and pathological parameters and Mann-Whitney U test for numerical parameters."}, {"asset": "source:pmid:27471570", "locator": "sections[6] \"Statistical Analyses\" paragraph 2", "quote": "For univariate survival analyses, Kaplan-Meier survival curves, with comparison by using log-rank test, were utilized."}, {"asset": "source:pmid:27471570", "locator": "sections[6] \"Statistical Analyses\" paragraph 2", "quote": "Parameters demonstrating P < .05 in univariate analyses were included in multivariate tests by using Cox proportional hazards regression."}], "state": "complete"}, {"id": "claim-data-access", "statement": "A transcriptomic dataset (GSE31684), comprising 93 radically resected UCB cases from GEO, NCBI, was selected for research; of these, 78 belonged to muscle-invasive tumors (pT2 to pT4) and 15 to non-muscle-invasive (pTa and pT1); 28 exhibited distant metastasis whereas 49 did not 29. In this data set, GeneChip® Human Genome U133 Plus 2.0 array (Affymetrix, Santa Clara, CA, USA) was used for analysis.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:27471570", "locator": "sections[3] \"Data Mining of Transcriptomic Database from GEO to Identify the Most Altered Gene\" paragraph 2", "quote": "A transcriptomic dataset (GSE31684), comprising 93 radically resected UCB cases from GEO, NCBI, was selected for research; of these, 78 belonged to muscle-invasive tumors (pT2 to pT4) and 15 to non-muscle-invasive (pTa and pT1); 28 exhibited distant metastasis whereas 49 did not 29. In this data set, GeneChip® Human Genome U133 Plus 2.0 array (Affymetrix, Santa Clara, CA, USA) was used for analysis."}], "state": "complete"}, {"id": "claim-target-result", "statement": "High THBS2 immunoexpression was associated with aggressive clinicopathological features and independently predicted worse disease-specific and metastasis-free survival in both UC-UUT and UCB groups.", "kind": "quantitative", "target": {"value": 0.05, "unit": "p-value", "tolerance": null, "source": "In multivariate analysis, THBS2 overexpression was an independent negative prognosticator that predicted unfavorable outcomes in both UC groups (all P < 0.05)."}, "evidence": [{"asset": "source:pmid:27471570", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "High THBS2 immunoexpression was significantly associated with advanced primary tumor status, nodal metastasis, and vascular invasion in both UC-UUT and UCB groups (all P ≤ .001)."}, {"asset": "source:pmid:27471570", "locator": "sections[12] \"Prognostic Impact of THBS2 Expression on UC-UUTs and UCBs\" paragraph 2", "quote": "In multivariate analysis, THBS2 overexpression was an independent negative prognosticator that predicted unfavorable outcomes in both UC groups (all P < 0.05)."}, {"asset": "source:pmid:27471570", "locator": "sections[6] \"Statistical Analyses\" paragraph 2", "quote": "We used SPSS Version 14.0 (SPSS Inc., Chicago, IL, USA) for statistical analysis."}, {"asset": "source:pmid:27471570", "locator": "sections[6] \"Statistical Analyses\" paragraph 2", "quote": "For univariate survival analyses, Kaplan-Meier survival curves, with comparison by using log-rank test, were utilized."}, {"asset": "source:pmid:27471570", "locator": "sections[6] \"Statistical Analyses\" paragraph 2", "quote": "Parameters demonstrating P < .05 in univariate analyses were included in multivariate tests by using Cox proportional hazards regression."}, {"asset": "source:pmid:27471570", "locator": "sections[3] \"Data Mining of Transcriptomic Database from GEO to Identify the Most Altered Gene\" paragraph 2", "quote": "After downloading the raw data, Nexus Expression 3 statistical software (BioDiscovery, El Segundo, CA, USA) was used to analyze all probe sets without filtering or preselection."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "High THBS2 immunoexpression was associated with aggressive clinicopathological features and independently predicted worse disease-specific and metastasis-free survival in both UC-UUT and UCB groups.", "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:27471570"], "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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MATERIALS AND METHODS: THBS2 immunostaining was performed in 340 UCs of upper urinary tr"], "order_basis": "paper_text_order:898", "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": ["We applied Pearson's chi-squared test to compare the association between THBS2 expression and miscellaneous critical categorical clinical and pathological parameters and Mann-Whitney U test for numerical parameters. For univariate survival analyses, Kaplan-Meier survival curves, with comparison by using log-rank test, were utilized. Parameters demonstrating P < .05 in univariate analyses were included in multivariate tests by using Cox proportional hazards regression."], "order_basis": "consumes_earlier_output", "id": "assay:2"}]}