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pmid:34733654

The prognostic roles of CYP19A1 expression in bladder cancer patients of different genders.

Shanghua Cai · Yuanfa Feng · Jianheng Ye · Yulin Deng · Zhiduan Cai · Xuejin Zhu · Ren Liu · Yixun Zhang · Zhihao Zou · Zhenfeng Tang · Zhaodong Han · Chi Tin Hon · Weide Zhong · Huichan He

Translational andrology and urology · 2021 doi:10.21037/tau-21-400

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title
The prognostic roles of CYP19A1 expression in bladder cancer patients of different genders.
doi
10.21037/tau-21-400
pmid
34733654
authors array · 14 items
[0]
Shanghua Cai
[1]
Yuanfa Feng
[2]
Jianheng Ye
[3]
Yulin Deng
[4]
Zhiduan Cai
[5]
Xuejin Zhu
[6]
Ren Liu
[7]
Yixun Zhang
[8]
Zhihao Zou
[9]
Zhenfeng Tang
[10]
Zhaodong Han
[11]
Chi Tin Hon
[12]
Weide Zhong
[13]
Huichan He
journal
Translational andrology and urology
year
2021
abstract
BACKGROUND: The incidence of bladder cancer (BCa) in male is approximately three to four times higher than in female, but the oncological outcomes in female patients with BCa are significantly worse than in male patients. Although many biomarkers have been identified in recent decades to predict the prognosis of BCa patients, few of them are able to distinguish the prognosis of BCa patients with gender difference. Aromatase encoded by the CYP19A1 gene catalyzes the conversion of androgens to estrogens. In this study, we investigate the prognosis significance of CYP19A1 expression considering the gender difference in BCa patients from four available public databases. METHODS: Four available public databases of BCa, including GSE13507, TCGA-BLCA, E-MTAB-4321, and E-MTAB-1803, were utilized in this analysis. The overall survival (OS) and progression-free survival (PFS) in different stages and genders were evaluated using the Kaplan-Meier analysis based on the optimal cut-off values of CYP19A1 expression. Then, Gene Set Enrichment Analysis (GSEA) were further performed to explore the potential biologic pathways by altering CYP19A1 expression in BCa patients. RESULTS: The results showed that patients with high CYP19A1 expression had a poorer outcome compared with those with low expression in both BCa cohorts in general. Higher CYP19A1 expression in male patients were significantly associated with shorter survival for either non-muscle-invasive bladder cancer (NMIBC) or muscle-invasive bladder cancer (MIBC). However, female NMIBC patients with high CYP19A1 expression were identified to have a better prognosis, whereas high CYP19A1 expression in female MIBC patients were significantly associated with poorer survival. The result of the GSEA showed that different outcomes in female and male patients with NMIBC were related to the interaction of CYP19A1 and the cell-cycle-related pathways. CONCLUSIONS: These findings demonstrated that CYP19A1 expression might have a potential role in distinguishing the prognosis of female BCa patients dependent on tumor stage. Our results provide new insights for aromatase-mediated BCa therapy.
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The OS and progression-free survival (PFS) were evaluated using the Kaplan-Meier method and the log-rank test based on the cut-off values using the survminer R package.
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The paper names GSE13507, E-MTAB-4321, E-MTAB-1803 in Gene Expression Omnibus (GEO) and the accession resolves in the repository. No dataset was downloaded and no licence was read.
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The OS and progression-free survival (PFS) were evaluated using the Kaplan-Meier method and the log-rank test based on the cut-off values using the survminer R package.
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{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:34733654", "kind": "science-record", "revision": 5, "content_hash": "sha256:4dc329d7f5e5455f3e89336f6e21833d2961906032173a614db534cb0f4c632e", "created_at": "2026-11-01T17:36:24Z", "updated_at": "2026-11-01T22:47:48Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "The prognostic roles of CYP19A1 expression in bladder cancer patients of different genders.", "doi": "10.21037/tau-21-400", "pmid": "34733654", "authors": ["Shanghua Cai", "Yuanfa Feng", "Jianheng Ye", "Yulin Deng", "Zhiduan Cai", "Xuejin Zhu", "Ren Liu", "Yixun Zhang", "Zhihao Zou", "Zhenfeng Tang", "Zhaodong Han", "Chi Tin Hon", "Weide Zhong", "Huichan He"], "journal": "Translational andrology and urology", "year": 2021, "abstract": "BACKGROUND: The incidence of bladder cancer (BCa) in male is approximately three to four times higher than in female, but the oncological outcomes in female patients with BCa are significantly worse than in male patients. Although many biomarkers have been identified in recent decades to predict the prognosis of BCa patients, few of them are able to distinguish the prognosis of BCa patients with gender difference. Aromatase encoded by the CYP19A1 gene catalyzes the conversion of androgens to estrogens. In this study, we investigate the prognosis significance of CYP19A1 expression considering the gender difference in BCa patients from four available public databases.\nMETHODS: Four available public databases of BCa, including GSE13507, TCGA-BLCA, E-MTAB-4321, and E-MTAB-1803, were utilized in this analysis. The overall survival (OS) and progression-free survival (PFS) in different stages and genders were evaluated using the Kaplan-Meier analysis based on the optimal cut-off values of CYP19A1 expression. Then, Gene Set Enrichment Analysis (GSEA) were further performed to explore the potential biologic pathways by altering CYP19A1 expression in BCa patients.\nRESULTS: The results showed that patients with high CYP19A1 expression had a poorer outcome compared with those with low expression in both BCa cohorts in general. Higher CYP19A1 expression in male patients were significantly associated with shorter survival for either non-muscle-invasive bladder cancer (NMIBC) or muscle-invasive bladder cancer (MIBC). However, female NMIBC patients with high CYP19A1 expression were identified to have a better prognosis, whereas high CYP19A1 expression in female MIBC patients were significantly associated with poorer survival. The result of the GSEA showed that different outcomes in female and male patients with NMIBC were related to the interaction of CYP19A1 and the cell-cycle-related pathways.\nCONCLUSIONS: These findings demonstrated that CYP19A1 expression might have a potential role in distinguishing the prognosis of female BCa patients dependent on tumor stage. Our results provide new insights for aromatase-mediated BCa therapy.", "claims": [{"id": "claim-method", "statement": "The OS and progression-free survival (PFS) were evaluated using the Kaplan-Meier method and the log-rank test based on the cut-off values using the survminer R package.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34733654", "locator": "sections[5] \"Statistical analysis\" paragraph 2", "quote": "The OS and progression-free survival (PFS) were evaluated using the Kaplan-Meier method and the log-rank test based on the cut-off values using the survminer R package."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Four available BCa cohorts, namely, GSE13507, TCGA-BLCA (23), E-MTAB-4321, and E-MTAB-1803 databases, were obtained from the Gene Expression Omnibus (GEO, http://www.ncbi.nlm.nih.gov/geo/), The Cancer Genome Atlas (TCGA, https://tcga-data.nci.nih.gov/), and the ArrayExpress database (https://www.ebi.ac.uk/arrayexpress/).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34733654", "locator": "sections[3] \"Public databases\" paragraph 2", "quote": "Four available BCa cohorts, namely, GSE13507, TCGA-BLCA (23), E-MTAB-4321, and E-MTAB-1803 databases, were obtained from the Gene Expression Omnibus (GEO, http://www.ncbi.nlm.nih.gov/geo/), The Cancer Genome Atlas (TCGA, https://tcga-data.nci.nih.gov/), and the ArrayExpress database (https://www.ebi.ac.uk/arrayexpress/)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "", "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:34733654"], "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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No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["survival_km"], "assets": ["source:pmid:34733654", "data:geo:E-MTAB-1803"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:E-MTAB-1803"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T17:05:30Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": null}, "calls": 5, "usage": {"prompt_tokens": 8758, "completion_tokens": 1556, "cached_tokens": 128}}, "human_critique": null, "stages": [{"id": "extraction", "state": "complete", "reader": "MiniMax-M3.1-Flash", "provider": "minimax"}], "gaps": ["review.independent_reader", "review.machine_critique", "review.human_critique"]}, "execution": {"state": "absent", "status": "not_run", "mode": null, "runs": [], "gaps": ["execution.not_run"]}, "provenance": {"entities": [{"id": "pmid:34733654", "type": "paper", "label": "pmid:34733654"}, {"id": "source:pmid:34733654", "type": "manuscript", "label": "PMID 34733654 full text"}, {"id": "data:geo:E-MTAB-1803", "type": "dataset", "label": "GEO E-MTAB-1803"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:34733654", "type": "paper", "label": "pmid:34733654"}, {"id": "source:pmid:34733654", "type": "manuscript", "label": "PMID 34733654 full text"}, {"id": "data:geo:E-MTAB-1803", "type": "dataset", "label": "GEO E-MTAB-1803"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-34733654", "type": "extraction", "used": ["source:pmid:34733654"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-E-MTAB-1803", "type": "accession_resolution", "used": ["data:geo:E-MTAB-1803"], "agent": "agent:corpus-assay-engine"}], "agents": [{"id": "agent:corpus-assay-engine", "type": "software", "label": "Corpus assay engine"}, {"id": "agent:minimax-reader", "type": "software", "label": "MiniMax literature reader"}], "source_run_id": "reading-sci-2026-11-01", "dsl_catalogue_fingerprint": "343fb30756ba6ec3", "capability_table_fingerprint": "2cb3e42f047d2ecf", "snapshot_id": "ba34b49490d9bfaf"}, "lineage": {"parent_id": "pmid:34733654", "parent_hash": "sha256:bafa4289ea7e76e4d055e881693f94fcbc9cc8f7ccae9f67e19b956161c25b25", "fork_of": null, "generation": 4}, "gaps": ["asset:data:geo:E-MTAB-1803 licence not read", "asset:data:geo:E-MTAB-1803 not downloaded", "asset:data:geo:E-MTAB-4321 licence not read", "asset:data:geo:E-MTAB-4321 not downloaded", "asset:data:geo:GSE13507 licence not read", "asset:data:geo:GSE13507 not downloaded", "execution.not_run", "method.reader_differs_from_extractor", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "analysis", "definition_id": "survival_analysis", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["survival_km"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["The OS and progression-free survival (PFS) were evaluated using the Kaplan-Meier method and the log-rank test based on the cut-off values using the survminer R package."], "order_basis": "analysis_only", "id": "assay:1"}]}