Proteomics of liquid biopsies: Depicting RCC infiltration into the renal vein by MS analysis of urine and plasma

Abstract

Liquid biopsies, as blood and urine, could offer an invaluable, easily accessible source of biomarkers, and evidences for elucidating the pathological processes. Only few studies integrated the proteomes driven by more than one biofluid. Furthermore, it is not clear which biofluid better mirrors the alterations triggered by disease. Venous infiltrating RCC(Renal Cell Carcinoma) could represent an advantageous model for exploring this aspect. Herein, we investigate how blood and urine "proteomically" reflect the changes occurring during RCC infiltration into renal vein(RV) by label-free nLC-ESI-MS/MS. We found 574 and 58 differentially expressed proteins(DEPs) in response to vascular involvement. To the augment of vascular involvement, the abundance of only three proteins in urine(UROM,RALA,CNDP1) and two in plasma(APOA1,K2C1) diminished while increased for twenty-six urinary proteins. 80 proteins were found both in urine and plasma, among which twenty-eight were DEPs. A huge overlap between the two biofluids was highlighted, as expected, being urine the filtrate of blood. However, this consistency decreases when RV-occlusion occurs suggesting alternative protein releases, and a loss of kidney architecture. Moreover, several proteomic and functional signatures were biofluid-specific. In conclusion, the complementarity between the specimens allowed to achieve a deeper level of molecular complexity of the RCC venous infiltration. SIGNIFICANCE: Although plasma and urine are strongly interconnected, only few proteomic studies investigated the complementarity of these fluids as bio-sources of information. Moreover, none of them was focused to their analysis and comparison in the context of vascular infiltration of renal cancer. Herein, new insights were gained regarding the impact into urinary and plasma proteome of the changes triggered by the ccRCC invasion into vascular system and renal vein. Furthermore, the integration of the information driven by the two liquid biopsies permits to unravel biological processes otherwise lost.

Keywords: Mass spectrometry; Plasma; Proteomics; Renal cell carcinoma; Renal vein invasion; Urine.