The impact of advanced proteomics in the search for markers and therapeutic targets of bladder cancer

Abstract

Bladder cancer is the most common cancer of the urinary tract and can be avoided through proper surveillance and monitoring. Several genetic factors are known to contribute to the progression of bladder cancer, many of which produce molecules that serve as cancer biomarkers. Blood, urine, and tissue are commonly analyzed for the presence of biomarkers, which can be derived from either the nucleus or the mitochondria. Recent advances in proteomics have facilitated the high-throughput profiling of data generated from bladder cancer-related proteins or peptides in parallel with high sensitivity and specificity, providing a wealth of information for biomarker discovery and validation. However, the transmission of screening results from one laboratory to another remains the main disadvantage of these methods, a fact that emphasizes the need for consistent and standardized procedures as suggested by the Human Proteome Organization. This review summarizes the latest discoveries and progress of biomarker identification for the early diagnosis, projected prognosis, and therapeutic response of bladder cancer, informs the readers of the current status of proteomic-based biomarker findings, and suggests avenues for future work.

Glycoproteomics identifies HOMER3 as a potentially targetable biomarker triggered by hypoxia and glucose deprivation in bladder cancer

“…The cell membrane proteome constitutes an important source of potentially targetable biomarkers, easily accessible to antibodies and other ligands [ 4 ]. The membrane proteome of cancer cells reflects their genetic, epigenetic, and transcriptomic instability, while actively contributing to all cancer hallmarks and disease progression [ 5 ].…”

Comprehensive Urinomic Identification of Protein Alternatives to Creatinine Normalization for Diagnostic Assessment of Lupus Nephritis

“…The utility of having such a normalizer protein for calibration of urine biomarkers extends beyond lupus nephritis. Urine biomarker testing is widely used for assessing cancers ( 1 – 4 ), multiple renal diseases ( 5 – 7 ), and other diseases ( 26 ) as well as for drug testing ( 27 ). Even when total protein in urine is assayed in clinical diagnostics, it is normalized to creatinine, in the form of the ACR test.…”

“…Excessive protein in the urine is an indication of the glomerular filtration barrier becoming compromised, and hence, this is a commonly used marker of renal disease. In addition to assaying total urine protein, specific urine proteins (and metabolites) are interrogated for countless diseases including bladder, prostate, and renal cancer ( 1 – 4 ), drug screening for addiction and therapeutic monitoring, acute kidney injury ( 5 ), chronic kidney disease ( 6 ), and lupus nephritis ( 7 ) and other genitourinary and gynecological conditions. To correctly interpret urine biomarker data, one needs to account for the hydration status of the patient.…”

Biomarker discovery and beyond for diagnosis of bladder diseases

“…Recent new types of software are being developed to create workflows that involve distinguishing biomarkers via integrated comparative and quantitative analysis [15]. Advanced proteomic analysis has led to high-throughput profiling of bladder cancer-related proteins with both high sensitivity and specificity, which has resulted in a wealth of informative biomarkers [16]. A similar strategy was utilized in a recent study that identified 54 potential protein biomarkers of bladder schistosomiasis by quantitatively comparing urinary samples from humans [17].…”