Ten Years of Proteomics in Bladder Cancer: Progress and Future Directions.

Research efforts targeting the identification of bladder cancer biomarkers have been extensive during the past decade. Investigations have been performed at the genome, transcriptome, proteome, and metabolome levels and outputs have started appearing including the sketching of disease molecular subtypes. Proteins are directly linked to cell phenotype hence they accumulate special interest as both biomarkers and therapeutic targets. Multiple technical challenges exist, of the main, being the protein concentration vast dynamic range and presence of proteins in modified forms. The scope of this review is to summarize the contribution of proteomics research in this quest of bladder cancer biomarkers. To obtain an unbiased and comprehensive overview, the scientific literature was searched for manuscripts describing proteomic studies on urothelial cancer from the last ten years and those including independent verification studies in urine, tissue and blood are briefly presented. General observations include: a) in most cases, suboptimal experimental design including healthy controls in biomarker discovery and frequently biomarker verification, is followed; b) variability in protein findings between studies can be observed, to some extent reflecting complexity of experimental approaches and proteome itself; c) consistently reported biomarkers include mainly plasma proteins and d) compilation of protein markers into diagnostic panels appears the most promising way forward. Two main avenues of research can now be foreseen: targeting integration of the existing disparate data with proteomic findings being placed in the context of existing knowledge on bladder cancer subtypes and in parallel, accumulation of clinical samples to support proper validation studies of promising marker combinations.