Proteomics and succinylation modification characterization in clear cell renal cell carcinoma

Clear cell renal cell carcinoma (ccRCC) represents the most lethal form of kidney cancer, with a significant number of patients experiencing tumor progression. Succinylation modification is a novel post-translational modification (PTM) that refers to modifying a protein with a succinyl group, which most frequently happens to lysine residues. Recent studies have revealed that abnormal succinylation, altered protein activity, dysfunctional roles in energy metabolism, and subsequent epigenetic modifications are linked to the onset and progression of conditions like inflammation, cancer, and other diseases. No studies have offered a comprehensive analysis of succinylation modification in ccRCC or clarified the mechanisms by which this modification operates within disease progression. In this study, we applied quantitative proteomics and succinylation modification omics to extensively examine the global proteome and succinylation modification changes in ccRCC tissues. Using high-throughput liquid chromatography-mass spectrometry, we identified 4801 lysine succinylation modification sites across 1274 proteins in ccRCC and adjacent non-cancerous tissues. Additionally, 434 succinylation sites within 328 proteins displayed significant differential modification in ccRCC (fold change (FC) > 1.5 or p < 0.05). Notably, the succinylated proteins were primarily associated with energy metabolism pathways, including fatty acid elongation, glyoxylate and dicarboxylate metabolism, the tricarboxylic acid cycle, and oxidative phosphorylation, and were predominantly located within the mitochondria. This study is the first to present a global proteomic profile and a detailed succinylation modification landscape in ccRCC. These findings introduce new potential approaches for treating ccRCC by reversing abnormal succinylation modifications.