Abstract
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.
Highlights
Bladder cancer (BC) is the sixth most common cancer diagnosis in the United States and is over four times more common in men than women [1, 2]
Of the 16 proteins screened by Luminex, 12 were within the detectable range and among these, 10 urine biomarkers showed significant elevation in bladder cancer (BC) compared to the controls
10 biomarkers showed a significant increase in BC compared to the urology clinic controls (Figure 1)
Summary
Bladder cancer (BC) is the sixth most common cancer diagnosis in the United States and is over four times more common in men than women [1, 2]. The most common diagnostic methods for BC include cytology and cystoscopy. Urine cystoscopy is currently the “gold standard” for diagnosis of BC. It is relatively invasive, expensive, and can potentially cause urinary tract infections. Urine cytology is a non-invasive method most commonly used for the surveillance of BC, but it is not recommended in initial disease evaluation [7]. It exhibits high specificity for high-grade tumors (~86%), it has poor sensitivity for low-grade tumors (~16%) (2). For BC patients presenting with lowgrade tumors with high rates of recurrence, this diagnostic modality may not be reliable for diagnosis [8]
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