Abstract
Purpose: To explore the tumor proteome of patients diagnosed with localized clear cell renal cancer (ccRCC) and treated with surgery. Material and methods: 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. Results: We identified and quantified 3091 proteins, including 2026 high-confidence proteins. Two proteomics subtypes of ccRCC (CC1 and CC2) were identified by CC using the high-confidence proteins only. Characterization of molecular differences between CC1 and CC2 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 CC1 were mainly related to translation and ribosome, while proteins overexpressed in CC2 were mainly related to focal adhesion and membrane. Second, a functional analysis using probabilistic graphical models was performed. CC1 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 CC2 subtype showed higher expression of proteins involved in focal adhesion, extracellular matrix, and collagen organization. Conclusions: ccRCC tumors can be classified in two different proteomics subtypes. CC1 and CC2 present specific proteomics profiles, reflecting alterations of different molecular pathways in each subtype. The knowledge generated in this type of studies could help in the development of new drugs targeting subtype-specific deregulated pathways.
Funder
EPIC-XS
Horizon 2020 program of the European Union
Consejería de Educación e Investigación de la Comunidad de Madrid
the Spanish Economy and Competitiveness Ministry
Reference38 articles.
1. Cancer statistics, 2022;Siegel;CA Cancer J. Clin.,2022
2. Surveillance after radical or partial nephrectomy for localized renal cell carcinoma and management of recurrent disease;Janzen;Urol. Clin. N. Am.,2003
3. Adjuvant therapy in renal cell carcinoma-past, present, and future;Janowitz;Semin. Oncol.,2013
4. Nivolumab plus Cabozantinib versus Sunitinib for Advanced Renal-Cell Carcinoma;Choueiri;N. Engl. J. Med.,2021
5. Atezolizumab plus bevacizumab versus sunitinib in patients with previously untreated metastatic renal cell carcinoma (IMmotion151): A multicentre, open-label, phase 3, randomised controlled trial;Rini;Lancet,2019