Exploring bladder cancer through urinary microbiota: innovative “urinetypes” classification and establishment of a diagnostic model

Abstract Background Bladder cancer (BCa) is a prevalent and lethal malignancy of the urinary system. Recent evidence suggests a strong association between the urinary microbiota and the pathogenesis, progression, and prognosis of BCa. This study investigated the role of the urinary microbiota in BCa...

Full description

Saved in:
Bibliographic Details
Main Authors: Zhaoyang Sheng, Jing Liu, Maoyu Wang, Xiang Chen, Jinshan Xu, Chen Zhang, Yang Xu, Hui Zhang, Jinpeng Zhu, Nan Qin, ShuXiong Zeng, Zhijun Zheng, ZhenSheng Zhang
Format: Article
Language:English
Published: BMC 2025-07-01
Series:Journal of Translational Medicine
Subjects:
Online Access:https://doi.org/10.1186/s12967-025-06518-y
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1849234840384176128
author Zhaoyang Sheng
Jing Liu
Maoyu Wang
Xiang Chen
Jinshan Xu
Chen Zhang
Yang Xu
Hui Zhang
Jinpeng Zhu
Nan Qin
ShuXiong Zeng
Zhijun Zheng
ZhenSheng Zhang
author_facet Zhaoyang Sheng
Jing Liu
Maoyu Wang
Xiang Chen
Jinshan Xu
Chen Zhang
Yang Xu
Hui Zhang
Jinpeng Zhu
Nan Qin
ShuXiong Zeng
Zhijun Zheng
ZhenSheng Zhang
author_sort Zhaoyang Sheng
collection DOAJ
description Abstract Background Bladder cancer (BCa) is a prevalent and lethal malignancy of the urinary system. Recent evidence suggests a strong association between the urinary microbiota and the pathogenesis, progression, and prognosis of BCa. This study investigated the role of the urinary microbiota in BCa, aiming to develop a non-invasive diagnostic model based on microbial biomarkers. Additionally, we proposed a novel urine-based microbiota classification method to enhance diagnostic accuracy and guide treatment strategies. Methods The study included a discovery cohort (104 BCa patients, 56 with Other Malignant Urological Cancer, 98 with benign urinary diseases, and 42 healthy controls) and a validation cohort (66 BCa patients, 5 with Other Malignant Urological Cancer, 51 with benign urinary diseases, and 22 healthy controls). The urinary microbiota composition was analyzed using 16 S rRNA gene sequencing to assess diversity, identify biomarkers, and construct a diagnostic model for BCa. Finally, clustering analysis was used to establish “Urinetypes”. Results BCa patients exhibited greater richness and diversity in their urinary microbiota, with significant differences in beta diversity observed across the groups. Genera such as Sphingomonas, Anaerococcus, Acinetobacter, Stenotrophomonas, Aeromonas, and Novosphingobium were more abundant in BCa patients, while Lactobacillus and Gardnerella were less abundant, suggesting their potential as biomarkers. PICRUSt analysis revealed significant enrichment in carbohydrate and nucleotide metabolism in BCa patients, reflecting the increased metabolic demands of cancer cells. A biomarker prediction model employing random forest analysis based on 12 microbial genera achieved high accuracy in the discovery cohort (AUC = 89.08%) and demonstrated robust performance in the validation cohort (AUC = 70.8%). To facilitate potential clinical application, we developed a “Patient Differentiation Index” (PDI), which maintained predictive efficiency in both the discovery cohort (AUC = 86.17%) and the validation cohort (AUC = 78%). Additionally, we identified distinct “Urinetypes”, including those dominated by Prevotella and Corynebacterium, which were more prevalent in BCa patients and might represent high-risk subtypes. Conclusion This study characterizes the urinary microbiota of BCa patients and, for the first time, provides a reliable non-invasive diagnostic method based on urinary microbiota. The introduction of the innovative concept of “Urinetypes” and the identification of high-risk subtypes associated with BCa offer the potential for improved diagnostic and therapeutic strategies. Trial registration This trial was registered on the Chinese Clinical Trial Registry (ChiCTR) with the registration number ChiCTR2300070969, registered on 27 April 2023, https://www.chictr.org.cn/ ChiCTR2300070969. The registration details are publicly accessible on ChiCTR for verification and reference.
format Article
id doaj-art-3f0a70c8a17a4de8b76209582db049b7
institution Kabale University
issn 1479-5876
language English
publishDate 2025-07-01
publisher BMC
record_format Article
series Journal of Translational Medicine
spelling doaj-art-3f0a70c8a17a4de8b76209582db049b72025-08-20T04:03:01ZengBMCJournal of Translational Medicine1479-58762025-07-0123111910.1186/s12967-025-06518-yExploring bladder cancer through urinary microbiota: innovative “urinetypes” classification and establishment of a diagnostic modelZhaoyang Sheng0Jing Liu1Maoyu Wang2Xiang Chen3Jinshan Xu4Chen Zhang5Yang Xu6Hui Zhang7Jinpeng Zhu8Nan Qin9ShuXiong Zeng10Zhijun Zheng11ZhenSheng Zhang12Department of Urology, Shanghai Changhai Hospital, Naval Medical UniversityRealbio Genomics InstituteDepartment of Urology, Shanghai Changhai Hospital, Naval Medical UniversityRealbio Genomics InstituteDepartment of Urology, Shanghai Changhai Hospital, Naval Medical UniversityDepartment of Urology, Shanghai Changhai Hospital, Naval Medical UniversityDepartment of Urology, Shanghai Changhai Hospital, Naval Medical UniversityDepartment of Urology, Shanghai Changhai Hospital, Naval Medical UniversityDepartment of Urology, Shanghai Changhai Hospital, Naval Medical UniversityRealbio Genomics InstituteDepartment of Urology, Shanghai Changhai Hospital, Naval Medical UniversityRealbio Genomics InstituteDepartment of Urology, Shanghai Changhai Hospital, Naval Medical UniversityAbstract Background Bladder cancer (BCa) is a prevalent and lethal malignancy of the urinary system. Recent evidence suggests a strong association between the urinary microbiota and the pathogenesis, progression, and prognosis of BCa. This study investigated the role of the urinary microbiota in BCa, aiming to develop a non-invasive diagnostic model based on microbial biomarkers. Additionally, we proposed a novel urine-based microbiota classification method to enhance diagnostic accuracy and guide treatment strategies. Methods The study included a discovery cohort (104 BCa patients, 56 with Other Malignant Urological Cancer, 98 with benign urinary diseases, and 42 healthy controls) and a validation cohort (66 BCa patients, 5 with Other Malignant Urological Cancer, 51 with benign urinary diseases, and 22 healthy controls). The urinary microbiota composition was analyzed using 16 S rRNA gene sequencing to assess diversity, identify biomarkers, and construct a diagnostic model for BCa. Finally, clustering analysis was used to establish “Urinetypes”. Results BCa patients exhibited greater richness and diversity in their urinary microbiota, with significant differences in beta diversity observed across the groups. Genera such as Sphingomonas, Anaerococcus, Acinetobacter, Stenotrophomonas, Aeromonas, and Novosphingobium were more abundant in BCa patients, while Lactobacillus and Gardnerella were less abundant, suggesting their potential as biomarkers. PICRUSt analysis revealed significant enrichment in carbohydrate and nucleotide metabolism in BCa patients, reflecting the increased metabolic demands of cancer cells. A biomarker prediction model employing random forest analysis based on 12 microbial genera achieved high accuracy in the discovery cohort (AUC = 89.08%) and demonstrated robust performance in the validation cohort (AUC = 70.8%). To facilitate potential clinical application, we developed a “Patient Differentiation Index” (PDI), which maintained predictive efficiency in both the discovery cohort (AUC = 86.17%) and the validation cohort (AUC = 78%). Additionally, we identified distinct “Urinetypes”, including those dominated by Prevotella and Corynebacterium, which were more prevalent in BCa patients and might represent high-risk subtypes. Conclusion This study characterizes the urinary microbiota of BCa patients and, for the first time, provides a reliable non-invasive diagnostic method based on urinary microbiota. The introduction of the innovative concept of “Urinetypes” and the identification of high-risk subtypes associated with BCa offer the potential for improved diagnostic and therapeutic strategies. Trial registration This trial was registered on the Chinese Clinical Trial Registry (ChiCTR) with the registration number ChiCTR2300070969, registered on 27 April 2023, https://www.chictr.org.cn/ ChiCTR2300070969. The registration details are publicly accessible on ChiCTR for verification and reference.https://doi.org/10.1186/s12967-025-06518-yBladder cancerUrinary microbiotaDiagnosisTypingBiomarkerCharacteristics
spellingShingle Zhaoyang Sheng
Jing Liu
Maoyu Wang
Xiang Chen
Jinshan Xu
Chen Zhang
Yang Xu
Hui Zhang
Jinpeng Zhu
Nan Qin
ShuXiong Zeng
Zhijun Zheng
ZhenSheng Zhang
Exploring bladder cancer through urinary microbiota: innovative “urinetypes” classification and establishment of a diagnostic model
Journal of Translational Medicine
Bladder cancer
Urinary microbiota
Diagnosis
Typing
Biomarker
Characteristics
title Exploring bladder cancer through urinary microbiota: innovative “urinetypes” classification and establishment of a diagnostic model
title_full Exploring bladder cancer through urinary microbiota: innovative “urinetypes” classification and establishment of a diagnostic model
title_fullStr Exploring bladder cancer through urinary microbiota: innovative “urinetypes” classification and establishment of a diagnostic model
title_full_unstemmed Exploring bladder cancer through urinary microbiota: innovative “urinetypes” classification and establishment of a diagnostic model
title_short Exploring bladder cancer through urinary microbiota: innovative “urinetypes” classification and establishment of a diagnostic model
title_sort exploring bladder cancer through urinary microbiota innovative urinetypes classification and establishment of a diagnostic model
topic Bladder cancer
Urinary microbiota
Diagnosis
Typing
Biomarker
Characteristics
url https://doi.org/10.1186/s12967-025-06518-y
work_keys_str_mv AT zhaoyangsheng exploringbladdercancerthroughurinarymicrobiotainnovativeurinetypesclassificationandestablishmentofadiagnosticmodel
AT jingliu exploringbladdercancerthroughurinarymicrobiotainnovativeurinetypesclassificationandestablishmentofadiagnosticmodel
AT maoyuwang exploringbladdercancerthroughurinarymicrobiotainnovativeurinetypesclassificationandestablishmentofadiagnosticmodel
AT xiangchen exploringbladdercancerthroughurinarymicrobiotainnovativeurinetypesclassificationandestablishmentofadiagnosticmodel
AT jinshanxu exploringbladdercancerthroughurinarymicrobiotainnovativeurinetypesclassificationandestablishmentofadiagnosticmodel
AT chenzhang exploringbladdercancerthroughurinarymicrobiotainnovativeurinetypesclassificationandestablishmentofadiagnosticmodel
AT yangxu exploringbladdercancerthroughurinarymicrobiotainnovativeurinetypesclassificationandestablishmentofadiagnosticmodel
AT huizhang exploringbladdercancerthroughurinarymicrobiotainnovativeurinetypesclassificationandestablishmentofadiagnosticmodel
AT jinpengzhu exploringbladdercancerthroughurinarymicrobiotainnovativeurinetypesclassificationandestablishmentofadiagnosticmodel
AT nanqin exploringbladdercancerthroughurinarymicrobiotainnovativeurinetypesclassificationandestablishmentofadiagnosticmodel
AT shuxiongzeng exploringbladdercancerthroughurinarymicrobiotainnovativeurinetypesclassificationandestablishmentofadiagnosticmodel
AT zhijunzheng exploringbladdercancerthroughurinarymicrobiotainnovativeurinetypesclassificationandestablishmentofadiagnosticmodel
AT zhenshengzhang exploringbladdercancerthroughurinarymicrobiotainnovativeurinetypesclassificationandestablishmentofadiagnosticmodel