Urine protein biomarkers of bladder cancer arising from 16-plex antibody-based screens
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Kamala Vanarsa1, Shereen Enan1, Pooja Patel1, Briony Strachan1, Anto Sam Crosslee Louis Sam Titus1, Aphrihl Dennis2, Yair Lotan2 and Chandra Mohan1
1 Department Biomedical Engineering, University of Houston, Houston, TX, USA
2 Department of Urology, UT Southwestern Medical Center, Dallas, TX, USA
Keywords: urothelial; proteomics; targeted screens; interleukins; inflammation
Received: November 13, 2020 Accepted: March 25, 2021 Published: April 13, 2021
Purpose: The purpose of this study is to identify novel urine protein biomarkers of bladder cancer using a Luminex based screening platform.
Materials and Methods: The current study examines urine samples from 66 subjects, comprised of 31 Urology clinic controls and 35 bladder cancer patients, using a Luminex based screening platform. ELISA validation was carried out for the top 4 prospective urine biomarkers using an independent cohort of 20 Urology clinic controls and 60 bladder cancer (BC) subjects.
Results: Of the 16 proteins screened by Luminex, 10 showed significant elevation in BC compared to the controls. Eight of these urine proteins were able to differentiate BC from control urine with ROC AUC values exceeding 0.70 at p < 0.0001, with specificity values exceeding 0.9. Upon ELISA validation, urine IL-1α, IL-1ra, and IL-8 were able to distinguish control urine from urine drawn from various bladder cancer stages, with IL-8 being the best discriminator. Compared to members of the IL-1 cytokine family, urine IL-8 was also best at discriminating T1 and/or T2–T4 from Ta BC (ROC AUC ≥ 0.83), as well as high grade from low grade BC (ROC AUC ≥ 0.82).
Conclusions: These findings suggest that urine IL-1α, IL-1ra and IL-8 are useful indicators of bladder cancer. Urine IL-8 not only distinguishes bladder cancer from controls, it also discriminates high grade from low grade disease, and the successive clinical stages of bladder cancer. While supportive of previous reports, these findings warrant further analysis in prospective cohorts.
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