Proteomics characterization of clear cell renal cell carcinoma

The aims of the study was to explore the tumor proteome of patients diagnosed with localized ccRCC and treated with surgery and the identification of altered pathways that could be the target of new treatments. A total of 165 FFPE tumor samples from patients diagnosed with ccRCC were analyzed using DIA-proteomics. Proteomics ccRCC subtypes were defined using a Consensus Cluster Algorithm (CCA) and characterized by a functional approach using probabilistic graphical models and survival analyses. Two proteomics subtypes of ccRCC (CCA1 and CCA2) were identified by CCA using the high confidence proteins only. Characterization of molecular differences between CCA1 and CCA2 was performed in two steps. First, we defined 514 proteins showing differential expression between the two subtypes using a significance analysis of microarrays analysis. Proteins overexpressed in CCA1 were mainly related to translation and ribosome, while proteins overexpressed in CCA2 were mainly related to focal adhesion and membrane. Second, a functional analysis using probabilistic graphical models was performed. The CCA1 subtype is characterized by an increased expression of proteins related to glycolysis, mitochondria, translation, adhesion proteins related to cytoskeleton and actin, nucleosome, and spliceosome, while CCA2 subtype showed higher expression o proteins involved in focal adhesion, extracellular matrix and collagen organization.