Proteomic analysis reveals distinctive protein expression patterns of thrombus in clear cell renal cell carcinoma

Abstract

Clear cell renal cell carcinoma (ccRCC) is a type of malignant tumor of the urinary system. The renal vein or vena cava thrombus can be found in a subset of ccRCC patients in whom it leads to worse prognosis. However, the protein expression profile and molecular features of ccRCC thrombus remain largely unclear. Here, a comparative proteomic analysis was performed using the 2D-LC-MS strategy for the thrombus-tumor-normal tissue triples of 15 ccRCC patients. Statistical analysis, GO enrichment analysis, protein-protein interaction network construction, and mRNA-based survival analysis were used to interpret the proteomic data. Three dysregulated proteins, GGT5 (gamma-glutamyl transferase 5), KRT7 (keratin 7) and CFHR1 (complement factor H related 1), were analyzed using western blot (WB) and immunohistochemistry (IHC) to validate the reliability of the proteomic analysis. The result of this analysis revealed 251 dysregulated proteins, which could be divided into 11 clusters depending on the changing trends, among the thrombus, tumor, and normal tissues. Several pathways and regulation networks were found to be associated with the thrombus, and some dysregulated proteins showed potential values for prognosis prediction. WB and IHC results were in accordance with the proteomic results, further validating the reliability of this study. In conclusion, our findings provide an overview of the thrombus at the molecular level as well as valuable information for further pathological studies or research on biomarkers and therapeutic targets.

Integrative transcriptome and proteome analyses of clear cell renal cell carcinoma develop a prognostic classifier associated with thrombus

“…Cheng et al claimed that the loss of the endosomal recycling protein Rab25 could promote tumor angiogenesis by modulating VEGF-A and VEGFR-1 expressions 26 , 27 . Low GGT5 (a protein with enzymatic activity) expression in renal tumors and thrombus tissues has also been reported in published research 28 . However, GGT5 regulation and its role in cancer remain unclear.…”