A urinary assay for mutation and methylation biomarkers in the diagnosis and recurrence prediction of non-muscle invasive bladder cancer patients
Abstract Background Currently, the clinical strategy for diagnosis of non-muscle invasive bladder cancer (NMIBC) such as cystoscopy and cytology are invasive and/or with limited accuracy. OncoUrine, a urinary assay for mutation and methylation biomarkers, have showed a high accuracy in the detection...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Language: | English |
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BMC
2023-09-01
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| Series: | BMC Medicine |
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| Online Access: | https://doi.org/10.1186/s12916-023-03065-5 |
| _version_ | 1827633996972949504 |
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| author | Hai Huang Ao Liu Yiming Liang Yaqun Xin Jiacheng Liu Yining Hao Da Huang Lu Chen Wei Li Guangliang Jiang Yuhua Huang Yaoting Xu Jie Zhang Tonghui Ma Danfeng Xu Yi Gao |
| author_facet | Hai Huang Ao Liu Yiming Liang Yaqun Xin Jiacheng Liu Yining Hao Da Huang Lu Chen Wei Li Guangliang Jiang Yuhua Huang Yaoting Xu Jie Zhang Tonghui Ma Danfeng Xu Yi Gao |
| author_sort | Hai Huang |
| collection | DOAJ |
| description | Abstract Background Currently, the clinical strategy for diagnosis of non-muscle invasive bladder cancer (NMIBC) such as cystoscopy and cytology are invasive and/or with limited accuracy. OncoUrine, a urinary assay for mutation and methylation biomarkers, have showed a high accuracy in the detection of upper tract urinary carcinoma (UTUC) patients with hematuria. The aim of this study is to evaluate the performance of OncoUrine in diagnosis of NMIBC patients. Methods In this multicenter prospective study, a total of 203 patients were enrolled, including 60 patients present with hematuria and 143 NMIBC patients under recurrence surveillance. Urine samples were collected before cystoscopy to undergo OncoUrine test. OncoUrine performance was calculated compared to clinical standard methods in hematuria cohort and recurrence surveillance cohort, respectively. Furthermore, NMIBC patients were followed up with a median time of 20.5 months (range 0.03 to 24.03 months) to assess the predictive value of OncoUrine during recurrence monitoring. Results For bladder cancer diagnosis, OncoUrine tested 47 samples and achieved a sensitivity/specificity/positive predictive value (PPV)/negative predictive value (NPV) of 80% (95% CI 44.2–96.5)/91.9% (95% CI 77.0–97.9)/72.7% (95% CI 39.3–92.7)/94.4% (95% CI 80.0–99.0) (kappa value 69.4%, 95% CI 44.4–94.3), indicating 72.3% of unnecessary cystoscopy. For recurrence diagnosis, OncoUrine tested 93 samples, and the sensitivity/specificity/PPV/NPV was 100% (95% CI 59.8–100.0)/68.2% (95% CI 57.1–77.7)/22.9% (95% CI 11.0–40.6)/100% (95% CI 92.3–100.0) (kappa value 27.0%, 95% CI 11.1–42.8), indicating 62.4% of spared cystoscopy. What is more, OncoUrine correctly predicted 80% (20/25) of final recurrence with 12/25 (48%) patients who were OncoUrine positive, but cystoscopy negative was followed with recurrence during follow-up. The test result of OncoUrine was also found significantly correlated with recurrence free survival (RFS) of NMIBC patients (median 34.4-month vs unreached; HR 6.0, 95% CI 2.7–13.5, P < 0.0001). Conclusions OncoUrine showed potential value to reduce the frequency of unnecessary cystoscopy and the healthcare cost of bladder cancer patients. Patients with positive test results represented a population who were at high risk of recurrence and thus should be subject to frequent surveillance to ensure timely detection of any potential recurrence. This study has been registered in ClinicalTrials.gov with the number NCT04994197 posted on August 2021. |
| first_indexed | 2024-03-09T15:08:14Z |
| format | Article |
| id | doaj.art-c7e51e84278c40399a782437c8dfc6d7 |
| institution | Directory Open Access Journal |
| issn | 1741-7015 |
| language | English |
| last_indexed | 2024-03-09T15:08:14Z |
| publishDate | 2023-09-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Medicine |
| spelling | doaj.art-c7e51e84278c40399a782437c8dfc6d72023-11-26T13:34:17ZengBMCBMC Medicine1741-70152023-09-0121111110.1186/s12916-023-03065-5A urinary assay for mutation and methylation biomarkers in the diagnosis and recurrence prediction of non-muscle invasive bladder cancer patientsHai Huang0Ao Liu1Yiming Liang2Yaqun Xin3Jiacheng Liu4Yining Hao5Da Huang6Lu Chen7Wei Li8Guangliang Jiang9Yuhua Huang10Yaoting Xu11Jie Zhang12Tonghui Ma13Danfeng Xu14Yi Gao15Department of Urology, Ruijin Hospital, Shanghai Jiaotong University School of MedicineDepartment of Urology, Ruijin Hospital, Shanghai Jiaotong University School of MedicineHangzhou Jichenjunchuang Medical Laboratory, Co., Ltd.Hangzhou Jichenjunchuang Medical Laboratory, Co., Ltd.Department of Urology, Ruijin Hospital, Shanghai Jiaotong University School of MedicineDepartment of Urology, Ruijin Hospital, Shanghai Jiaotong University School of MedicineDepartment of Urology, Ruijin Hospital, Shanghai Jiaotong University School of MedicineDepartment of Urology, Ruijin Hospital, Shanghai Jiaotong University School of MedicineHangzhou Jichenjunchuang Medical Laboratory, Co., Ltd.Department of Urology, Ruijin Hospital, Shanghai Jiaotong University School of MedicineDepartment of Urology, the First Affiliated Hospital of Soochow UniversityDepartment of Urologic Surgery, Shanghai Fourth People`S Hospital Affiliated to Tongji UniversityHangzhou Jichenjunchuang Medical Laboratory, Co., Ltd.Hangzhou Jichenjunchuang Medical Laboratory, Co., Ltd.Department of Urology, Ruijin Hospital, Shanghai Jiaotong University School of MedicineDepartment of Urology, Ruijin Hospital, Shanghai Jiaotong University School of MedicineAbstract Background Currently, the clinical strategy for diagnosis of non-muscle invasive bladder cancer (NMIBC) such as cystoscopy and cytology are invasive and/or with limited accuracy. OncoUrine, a urinary assay for mutation and methylation biomarkers, have showed a high accuracy in the detection of upper tract urinary carcinoma (UTUC) patients with hematuria. The aim of this study is to evaluate the performance of OncoUrine in diagnosis of NMIBC patients. Methods In this multicenter prospective study, a total of 203 patients were enrolled, including 60 patients present with hematuria and 143 NMIBC patients under recurrence surveillance. Urine samples were collected before cystoscopy to undergo OncoUrine test. OncoUrine performance was calculated compared to clinical standard methods in hematuria cohort and recurrence surveillance cohort, respectively. Furthermore, NMIBC patients were followed up with a median time of 20.5 months (range 0.03 to 24.03 months) to assess the predictive value of OncoUrine during recurrence monitoring. Results For bladder cancer diagnosis, OncoUrine tested 47 samples and achieved a sensitivity/specificity/positive predictive value (PPV)/negative predictive value (NPV) of 80% (95% CI 44.2–96.5)/91.9% (95% CI 77.0–97.9)/72.7% (95% CI 39.3–92.7)/94.4% (95% CI 80.0–99.0) (kappa value 69.4%, 95% CI 44.4–94.3), indicating 72.3% of unnecessary cystoscopy. For recurrence diagnosis, OncoUrine tested 93 samples, and the sensitivity/specificity/PPV/NPV was 100% (95% CI 59.8–100.0)/68.2% (95% CI 57.1–77.7)/22.9% (95% CI 11.0–40.6)/100% (95% CI 92.3–100.0) (kappa value 27.0%, 95% CI 11.1–42.8), indicating 62.4% of spared cystoscopy. What is more, OncoUrine correctly predicted 80% (20/25) of final recurrence with 12/25 (48%) patients who were OncoUrine positive, but cystoscopy negative was followed with recurrence during follow-up. The test result of OncoUrine was also found significantly correlated with recurrence free survival (RFS) of NMIBC patients (median 34.4-month vs unreached; HR 6.0, 95% CI 2.7–13.5, P < 0.0001). Conclusions OncoUrine showed potential value to reduce the frequency of unnecessary cystoscopy and the healthcare cost of bladder cancer patients. Patients with positive test results represented a population who were at high risk of recurrence and thus should be subject to frequent surveillance to ensure timely detection of any potential recurrence. This study has been registered in ClinicalTrials.gov with the number NCT04994197 posted on August 2021.https://doi.org/10.1186/s12916-023-03065-5Non-muscle invasive bladder cancerCystoscopyMutationMethylationDiagnosisRecurrence surveillance |
| spellingShingle | Hai Huang Ao Liu Yiming Liang Yaqun Xin Jiacheng Liu Yining Hao Da Huang Lu Chen Wei Li Guangliang Jiang Yuhua Huang Yaoting Xu Jie Zhang Tonghui Ma Danfeng Xu Yi Gao A urinary assay for mutation and methylation biomarkers in the diagnosis and recurrence prediction of non-muscle invasive bladder cancer patients BMC Medicine Non-muscle invasive bladder cancer Cystoscopy Mutation Methylation Diagnosis Recurrence surveillance |
| title | A urinary assay for mutation and methylation biomarkers in the diagnosis and recurrence prediction of non-muscle invasive bladder cancer patients |
| title_full | A urinary assay for mutation and methylation biomarkers in the diagnosis and recurrence prediction of non-muscle invasive bladder cancer patients |
| title_fullStr | A urinary assay for mutation and methylation biomarkers in the diagnosis and recurrence prediction of non-muscle invasive bladder cancer patients |
| title_full_unstemmed | A urinary assay for mutation and methylation biomarkers in the diagnosis and recurrence prediction of non-muscle invasive bladder cancer patients |
| title_short | A urinary assay for mutation and methylation biomarkers in the diagnosis and recurrence prediction of non-muscle invasive bladder cancer patients |
| title_sort | urinary assay for mutation and methylation biomarkers in the diagnosis and recurrence prediction of non muscle invasive bladder cancer patients |
| topic | Non-muscle invasive bladder cancer Cystoscopy Mutation Methylation Diagnosis Recurrence surveillance |
| url | https://doi.org/10.1186/s12916-023-03065-5 |
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