Proteomics Characterization of Clear Cell Renal Cell Carcinoma.

To explore the tumor proteome of patients diagnosed with localized clear cell renal cancer (ccRCC) and treated with surgery.

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.

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.

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.

Journal of clinical medicine. 2023 Jan 03*** epublish ***

Jesús Miranda-Poma, Lucía Trilla-Fuertes, Rocío López-Vacas, Elena López-Camacho, Eugenia García-Fernández, Ana Pertejo, María I Lumbreras-Herrera, Andrea Zapater-Moros, Mariana Díaz-Almirón, Antje Dittmann, Juan Ángel Fresno Vara, Enrique Espinosa, Pilar González-Peramato, Álvaro Pinto-Marín, Angelo Gámez-Pozo

Medical Oncology Service, Hospital Universitario Quironsalud Madrid, 28223 Madrid, Spain., Molecular Oncology Laboratory, Hospital Universitario La Paz-IdiPAZ, 28046 Madrid, Spain., Biomedica Molecular Medicine SL, 28049 Madrid, Spain., Department of Pathology, University Hospital La Paz, 28046 Madrid, Spain., Medical Oncology Service, Hospital Universitario La Paz, 28046 Madrid, Spain., Biostatistics Unit, Hospital Universitario La Paz-IdiPAZ, 28046 Madrid, Spain., Functional Genomics Center Zurich, 8057 Zurich, Switzerland.