Conclusion: Concluding Remarks and Perspectives
In this short review, we have provided information on the current state of 'omics' studies and available data sets relevant to bladder health and pathological condition, and presents opportunities for new research directed at understanding the pathogenesis of this complex condition. We believe that the ultimate goals of urine profiling of proteome and metabolome should be (i) to identify non-invasive diagnostic and prognostic biomarkers of bladder diseases, (ii) to better understand the biology of bladder diseases, and (iii) to determine the therapeutic strategies targeting the critical pathways of various bladder diseases. Recent efforts in the generation of large genomics, transcriptomics, proteomics, metabolomics, and other types of 'omics' data sets have provided a series of urinary biomarker candidates of bladder diseases. In spite of much efforts to identify candidate urinary biomarkers, it is still required to validate such markers in larger numbers of urine samples using targeted proteomics and metabolomics analyses in a prospective way.
Diagnostic and treatment modalities, even subjective diagnostic tools, are largely unavailable. As described here, our attempts to perform a systematic review and to build a pooled database using existing public 'omics' data associated with bladder health and various pathological conditions revealed the significant limitations and challenges facing investigators in the field. Many reports have suggested that natural diversity of patient population clearly plays a role in the difficulty of validating urine biomarkers. Expanding tests to include the general population often leads to loss or decrease in sensitivity. However, if tests are used for patients presenting specific symptoms in the clinic, and not for the general population, to inform about prognosis or treatment options, the pitfalls of general-population based urinary biomarkers may be alleviated. However, the cost of developing and validating a clinical grade assay is clearly beyond regular laboratory funding and would require concerted efforts by health agencies.
Collectively, despite these numerous pitfalls, urine is an interesting source of biomarkers for monitoring the bladder health. Rather than a single urinary molecular biomarker, a panel of biomarkers may be required to achieve the overall high level of specificity needed, so the trend is shifting towards implementing a panel of biomarkers, which may increase specificity. In order to translate potential biomarkers to clinical practice, vigorous validation must be pursued, with input from industry or large collaborative studies. Computational approaches combined with high quality 'omics' data could provide new insights in the field, essential molecular details about regulatory mechanisms and perturbations leading to bladder diseases, and essential information if we are to offer improved diagnostic capability and treatment strategies for patients.
APF: antiproliferative factor; BCa: bladder cancer; BPH: benign prostatic hyperplasia; DEPs: differentially expressed proteins; DFI/LC-MS/MS: direct flow injection mass spectrometry; EV: extracellular vesicles; GC-MS: gas chromatography mass spectrometry; HMDB: human metabolome database; HPLC: high performance liquid chromatography; IC: interstitial cystitis/pelvic bladder syndrome/bladder pain syndrome; ICP-MS: inductively coupled plasma mass spectrometry; iTRAQ: isobaric tags for relative and absolute quantitation; LC-MS: liquid chromatography-mass spectrometry; MALDITOF: matrix assisted laser desorption/ionization time-of-flight; MIBC: muscle invasive bladder cancer; MS: mass spectrometry; nano-MALDI-MS: nano-liquid chromatography-tandem mass spectrometry; NMIBC: non-muscle invasive bladder cancer; NMR: nuclear magnetic resonance spectroscopy; PCa: prostate cancer; PTMs: posttranslational modifications; SELDI-TOF: surface-enhanced laser desorption/ionization time-of-flight; SILAC: stable-isotope labeling by amino acids; SRM/MRM: selective or multiple Reaction monitoring
The authors would like to thank Dr. Oliver Fiehn (UC Davis) for careful review and editing the manuscript.
BMC Urol. 2016;16(11) © 2016 BioMed Central, Ltd.