Developing proteomic biomarkers for bladder cancer: towards clinical application

Abstract

Clinical use of proteomic biomarkers has the potential to substantially improve the outcomes of patients with bladder cancer. An unmet clinical need evidently exists for noninvasive biomarkers, which might enable improvements in both the diagnosis and prognosis of patients with bladder cancer, as well as improved monitoring of patients for the presence of recurrence. Urine is considered the optimal noninvasive source of proteomic biomarkers in patients with bladder cancer. Currently, a number of single-protein biomarkers have been detected in urine and tissue using a variety of proteomic techniques, each having specific conceptual considerations and technical implications. Promising preclinical data are available for several of these proteins; however, the combination of single urinary proteins into multimarker panels might better encompass the molecular heterogeneity of bladder cancer within this patient population, and prove more effective in clinical use.

Development and Validation of Urine-based Peptide Biomarker Panels for Detecting Bladder Cancer in a Multi-center Study

“…Considering the prevalence rates for the specific cohorts, the developed biomarker panels present an NPV value of 81.3% (95% CI, 68%-91%) and PPV value of 83.2 (95% CI, 75%-89%) for the primary and NPV of 93.6% (95% CI, 85%-98%) and PPV of 32.32% (95% CI, 23%-43%), for the follow-up cohorts. These performance rates are at least as good as those of other urothelial bladder cancer molecular markers which are FDA-approved and/or are currently under investigation (6). A direct comparison of different markers and their performance, as reported in various studies is difficult, mainly due to differences in the clinical design of the respective studies.…”

“…However, due to high urothelial bladder cancer relapse rates (4) frequent patient monitoring is required (3), leading to diminished patient compliance and augmented associated healthcare costs (5). In an effort to reduce the frequency of cystoscopies conducted, several noninvasive biomarkers have been approved by the FDA, albeit with performance rates remaining insufficient to replace current diagnostic and monitoring practices relying on cystoscopy (6). Therefore, a prevailing need for noninvasive biomarkers which will facilitate the timely diagnosis of primary and recurrent urothelial bladder cancer (6), including low-grade NMIBC (7,8), remains unmet to date.…”

“…In an effort to reduce the frequency of cystoscopies conducted, several noninvasive biomarkers have been approved by the FDA, albeit with performance rates remaining insufficient to replace current diagnostic and monitoring practices relying on cystoscopy (6). Therefore, a prevailing need for noninvasive biomarkers which will facilitate the timely diagnosis of primary and recurrent urothelial bladder cancer (6), including low-grade NMIBC (7,8), remains unmet to date. Such biomarkers are likely to reduce the frequency of diagnostic cystoscopies conducted, particularly among patients undergoing monitoring for recurrent urothelial bladder cancer.…”

Integrative Analysis of Multi-omics Data for Discovery and Functional Studies of Complex Human Diseases

“…Proteomics approach has been widely adopted in studies of human diseases including cancer (Frantzi et al, 2015; S. Pan, Brentnall, & Chen, 2015; Petricoin et al, 2002; Tsai et al, 2015), multiple sclerosis (Farias, Pradella, Schmitt, Santos, & Martins-de-Souza, 2014) and schizophrenia (Al Awam et al, 2015; Nascimento & Martins-de-Souza, 2015).…”

“…However, these studies have found many protein candidates, which can potentially improve prognosis, diagnosis, and effectiveness of treatment. More recent proteomic studies also used body fluid samples to identify protein markers for bladder cancer (Frantzi et al, 2015), pancreatic cancer (S. Pan et al, 2015) and hepatocellular carcinoma (Tsai et al, 2015).…”