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Abstract
Renal cell carcinomas, originating from the renal cortex, account for about 80% of kidney primary malignancies. Small localized tumors rarely produce symptoms and diagnosis is often delayed until the disease is advanced. In contrast to other urological cancers, renal cell carcinomas are associated with a high degree of metastases and a low 5-year survival rate. The identification of diagnostic and prognostic markers, especially in the urine, remains an area of intense investigation. Different proteomic strategies have been applied so far to biomarker discovery in urine at the proteome or the peptidome level. Gel-based and gel-free strategies combined with mass spectrometry are the most-used strategies, have different success rates, and will be depicted here. We also prefigure a scenario in which the limitations of a single approach are overcome by applying new and complementary research strategies, relying on the excellent availability coupled to the intrinsic richness typical of urine samples.
Financial & competing interests disclosure
The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
No writing assistance was utilized in the production of this manuscript.
Key issues
Renal cell carcinoma (RCC), arising from kidney tubules, accounts for 2–3% of malignant neoplasms in adults. Since early diagnosis and accurate prognosis are of primary importance for treatment and patients’ survival, this tumor being radio- and chemo-resistant, there is an urgent need for diagnostic and prognostic biomarkers.
Easy collection and manipulation of urine have prompted projects aimed at elucidation of their global proteome as a promising source of biomarkers for renal diseases.
Two-dimensional electrophoresis followed by MALDI-MS and/or LC-MS/MS and validation by western blotting represents the most widely used proteomic approach for the analysis of urine soluble proteins.
Such proteomic studies allowed identifying and validating several up- or down-regulated proteins in RCC patients’ urine; some of them had a correlation with the prognosis such as cathepsin D, or with the RCC type, stage or grade, such as aquaporin-1 and perlipin-2.
A new promising strategy concerns the isolation and the proteomic investigation of urinary exosomes, nanovesicles released from epithelial cells facing the urinary space, reflecting their protein composition.
Urinary proteome prefractionation techniques, such as SELDI and the use of magnetic beads, are usually required to increase the analysis outcomes of either small proteins or endogenous peptides.
The filter-aided sample preparation method has recently gained attention as it could allow the simultaneous investigation of both urinary proteome and peptidome.