Low expression of ZSCAN4 predicts unfavorable outcome in urothelial carcinoma of upper urinary tract and urinary bladder.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:36841776", "kind": "science-record", "revision": 3, "content_hash": "sha256:7cf30258486a7edeb34fc0ebd679f7cab3c673bd3537b9689d75c2c7223f2ac8", "created_at": "2026-11-01T19:01:27Z", "updated_at": "2026-11-01T22:51:22Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Low expression of ZSCAN4 predicts unfavorable outcome in urothelial carcinoma of upper urinary tract and urinary bladder.", "doi": "10.1186/s12957-023-02948-4", "pmid": "36841776", "authors": ["Hong-Lin He", "Hong-Yue Lai", "Ti-Chun Chan", "Chung-Hsi Hsing", "Steven K Huang", "Kun-Lin Hsieh", "Tzu-Ju Chen", "Wan-Shan Li", "Yu-Hsuan Kuo", "Yow-Ling Shiue", "Chien-Feng Li"], "journal": "World journal of surgical oncology", "year": 2023, "abstract": "BACKGROUND: With the advance in genome-wide analyses, genetic alternations have been found to play an important role in carcinogenesis and aggressiveness of UC. Through bioinformatic analysis of gene expression profiles of urinary bladder urothelial carcinoma (UBUC) from publicly available GEO dataset (GSE31684), Zinc finger and SCAN domain containing 4 (ZSCAN4) was identified as a significant downregulated gene in muscle-invasive bladder cancer when compared with non-muscle-invasive bladder cancer.\nMETHODS: The expression of ZSCAN4 was evaluated by immunohistochemistry in 340 upper urinary tract urothelial carcinomas (UTUCs) and 295 UBUCs. The expression profiles of ZSCAN4 and potential signaling pathways were analyzed bioinformatically.\nRESULTS: In UTUC, low expression of ZSCAN4 was significantly associated with advanced primary pT stage (P = 0.011), increased nodal metastasis (P = 0.002) and increased vascular invasion (P = 0.019). In UBUC, low expression of ZSCAN4 was significantly correlated with advanced primary pT stage (P < 0.001), increased nodal metastasis (P = 0.001), high histological grade (P = 0.003) and increased vascular invasion (P = 0.003). In survival analysis, low expression of ZSCAN4 acted as an independent negative prognostic factor for disease-specific survival and metastasis-free survival both in UTUC and UBUC. Gene ontology analysis showed that ZSCAN4 mRNA and its co-downregulated genes are associated with the mitotic cell cycle.\nCONCLUSIONS: Low expression of ZSCAN4 predicted worse outcome in urothelial carcinoma and might have potential regulatory role in cell mitosis.", "claims": [{"id": "claim-method", "statement": "For associations between immunohistochemical expression of ZSCAN4 and clinicopathological parameters, we used Pearson’s chi-squared test to identify significant differences between variables. Kaplan–Meier plots were applied to evaluate survival data, including disease-specific survival (DSS) and metastasis-free survival (MeFS). The prognostic significances of each parameter with suitable cut-offs were determined by the log-rank test. The Cox proportional hazards regression model was used to measure the effects of variables on survival rates.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36841776", "locator": "sections[7] \"Statistical analyses\" paragraph 2", "quote": "For associations between immunohistochemical expression of ZSCAN4 and clinicopathological parameters, we used Pearson’s chi-squared test to identify significant differences between variables. Kaplan–Meier plots were applied to evaluate survival data, including disease-specific survival (DSS) and metastasis-free survival (MeFS). The prognostic significances of each parameter with suitable cut-offs were determined by the log-rank test. The Cox proportional hazards regression model was used to measure the effects of variables on survival rates."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The data generated or analyzed in the current study were available from the corresponding author on reasonable request.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36841776", "locator": "sections[23] \"notes\" paragraph 1", "quote": "The data generated or analyzed in the current study were available from the corresponding author on reasonable request."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Low expression of ZSCAN4 predicted worse outcome in urothelial carcinoma and might have potential regulatory role in cell mitosis.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:36841776", "locator": "sections[0] \"Abstract\" paragraph 4", "quote": "Low expression of ZSCAN4 predicted worse outcome in urothelial carcinoma and might have potential regulatory role in cell mitosis."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Low expression of ZSCAN4 predicted worse outcome in urothelial carcinoma and might have potential regulatory role in cell mitosis.", "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:36841776"], "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:GSE31684"], "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:GSE31684"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:36841776", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1186/s12957-023-02948-4", "sha256": "sha256:4c24386cc658787a982616e9f020854d713ca8b312ae341fe0957145ee2eafa2", "bytes": 30250, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1186/s12957-023-02948-4", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC9960215", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE31684", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE31684", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE31684", "version": null, "note": "The data generated or analyzed in the current study were available from the corresponding author on reasonable request.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The data generated or analyzed in the current study were available from the corresponding author on reasonable request.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM786491", "GSM786492", "GSM786493", "GSM786494", "GSM786495", "GSM786496", "GSM786497", "GSM786498", "GSM786499", "GSM786500", "GSM786501", "GSM786502", "GSM786503", "GSM786504", "GSM786505", "GSM786506", "GSM786507", "GSM786508", "GSM786509", "GSM786510", "GSM786511", "GSM786512", "GSM786513", "GSM786514", "GSM786515", "GSM786516", "GSM786517", "GSM786518", "GSM786519", "GSM786520", "GSM786521", "GSM786522", "GSM786523", "GSM786524", "GSM786525", "GSM786526", "GSM786527", "GSM786528", "GSM786529", "GSM786530", "GSM786531", "GSM786532", "GSM786533", "GSM786534", "GSM786535", "GSM786536", "GSM786537", "GSM786538", "GSM786539", "GSM786540", "GSM786541", "GSM786542", "GSM786543", "GSM786544", "GSM786545", "GSM786546", "GSM786547", "GSM786548", "GSM786549", "GSM786550", "GSM786551", "GSM786552", "GSM786553", "GSM786554", "GSM786555", "GSM786556", "GSM786557", "GSM786558", "GSM786559", "GSM786560", "GSM786561", "GSM786562", "GSM786563", "GSM786564", "GSM786565", "GSM786566", "GSM786567", "GSM786568", "GSM786569", "GSM786570", "GSM786571", "GSM786572", "GSM786573", "GSM786574", "GSM786575", "GSM786576", "GSM786577", "GSM786578", "GSM786579", "GSM786580", "GSM786581", "GSM786582", "GSM786583"], "sample_count": 93, "group_sizes": null, "group_sizes_basis": null, "platform": "570", "taxon": "Homo sapiens", "title": "Combination of a novel gene expression signature with a clinical nomogram improves the prediction of survival in high-risk bladder cancer  ", "resolution_checked_at": "2026-11-01T15:39:54Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}], "gaps": ["asset:data:geo:GSE31684 not downloaded", "asset:data:geo:GSE31684 licence not read"]}, "analysis": {"state": "complete", "methods": [{"id": "method-1", "family": "survival_analysis", "specific": "cox_proportional_hazards", "label": "Survival analysis", "dsl_operations": ["cox_ph"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["time_to_event_with_censoring"], "evidence": {"score": 1.0, "band": "verbatim", "quote": "For associations between immunohistochemical expression of ZSCAN4 and clinicopathological parameters, we used Pearson’s chi-squared test to identify significant differences between variables. 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