Clinical evaluation of Bladder CARE, a new epigenetic test for bladder cancer detection in urine samples

Paolo Piatti, Yap Ching Chew, Michiko Suwoto, Taikun Yamada, Benjamin Jara, Xi Yu Jia, Wei Guo, Saum Ghodoussipour, Siamak Daneshmand, Hamed Ahmadi, Jeffrey Rice, Jeffrey Bhasin, Faith Holloway, Yvonne Tsai, Yoshitomo Chihara, Gangning Liang

Research output: Contribution to journalArticlepeer-review

10 Scopus citations


Background: Bladder cancer (BC) is the 5th most common cancer in the USA. Non-muscle invasive bladder cancer represents about 70% of all cases and has generally a favorable outcome. However, recurrence rates as high as 60 to 70% and progression rates of 10 to 20% necessitate intensive surveillance with cystoscopy. The invasiveness and high cost of cystoscopy poses significant burden on BC patients as well as on the healthcare system. In this study we test the feasibility of a simple, sensitive, and non-invasive detection of BC using Bladder CARE test in urine samples. Results: Urine from 136 healthy and 77 BC subjects was collected using the at-home Bladder CARE Urine Collection Kit and analyzed with Bladder CARE test. The test measures the methylation level of three BC-specific biomarkers and two internal controls using methylation-sensitive restriction enzymes coupled with qPCR. Bladder CARE showed an overall sensitivity of 93.5%, a specificity of 92.6%, and a PPV and NPV of 87.8% and 96.2%, respectively. Bladder CARE has an LOD as low as 0.046%, which equates to detecting 1 cancer cell for every 2,200 cells analyzed. We also provided evidence that bisulfite-free methods to assess DNA methylation, like Bladder CARE, are advantageous compared to conventional methods that rely on bisulfite conversion of the DNA. Conclusion: Highly sensitive detection of BC in urine samples is possible using Bladder CARE. The low LOD of the test and the measurement of epigenetic biomarkers make Bladder CARE a good candidate for the early detection of BC and possibly for the routine screening and surveillance of BC patients. Bladder CARE and the at-home urine sample collection system have the potential to (1) reduce unnecessary invasive testing for BC (2) reduce the burden of surveillance on patients and on the healthcare system, (3) improve the detection of early stage BC, and (4) allow physicians to streamline the monitoring of patients.

Original languageEnglish (US)
Article number84
JournalClinical epigenetics
Issue number1
StatePublished - Dec 2021
Externally publishedYes

Bibliographical note

Funding Information:
This research was coordinated by Zymo Research Corp. (Zymo) and by the Department of Urology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA. The research was sponsored through in-kind contributions (reagents and analyses necessary for the study) by Pangea Laboratory, LLC, and by Zymo. The study was supported by SC CTSI (received by G. Liang and S. Daneshmand), from Cure it Cancer Research (received by G. Liang and S. Daneshmand), and from The Vicky Joseph Cancer Research Foundation (received by G. Liang).

Publisher Copyright:
© 2021, The Author(s).


  • At-home sample collection
  • Bladder cancer
  • DNA methylation
  • Non-invasive testing
  • Urine


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