New Method Enhanced Extraction of Protein Signatures of Renal Cell Carcinoma from Proteomics Data

In this study, we generated label-free data-independent acquisition (DIA)-based liquid chromatography (LC)-mass spectrometry (MS) proteomics data from 261 renal cell carcinomas (RCC) and 195 normal adjacent tissues (NAT). The RCC tumors included 48 nonclear cell renal cell carcinomas (non-ccRCC) and 213 ccRCC. A total of 219,740 peptides and 11,943 protein groups were identified, with 9,787 protein groups per sample on average. We adopted a comprehensive approach to select representative samples with different mutations, considering histopathological, immune, methylation, and non-negative matrix factorization (NMF)-based subtypes, along with clinical characteristics (gender, grade, and stage) to capture the complexity and diversity of ccRCC tumors. We identified a protein signature containing 55 proteins that distinguish RCC tumors from NATs. Furthermore, a protein signature containing 39 proteins that differentiate different RCC tumor subtypes was also identified. Our findings offer an extensive perspective of the proteomic landscape in RCC, illuminating specific proteins that serve to distinguish RCC tumors from NATs and among various RCC tumor subtypes.