Label-Free Quantitative Proteomics of Renal Cell Carcinomas with Differential Hypoxia-Inducible Factor-2α Expression

摘要

228 high-fidelity protein identifications in the VHL-mutant RCCs 99 proteins regulated by VHL genotype in RCCs Label-free quantitative proteomics identified differentially expressed proteins due to distinct VHL genotypes with the use of TICs from identified MS/MS spectra (81 IDs) and extracted peptide ion (MS) intensities (46 IDs) in the workflow and resulted in a substantial improvement over our previously implemented spectral counting (22 IDs) methodology (Prokai et al., 2009) Differentially expressed proteins subjected to IPA analysis revealed VHL genotype regulated tumor energetics such as methylglyoxal degradation, glycolysis, and the pentose phosphate pathway in RCC cells. Down-regulation of key enzymes of glycolysis and the pentose phosphate pathway strongly indicated a possible metabolic shift towards glutaminolysis in VHL-mut RCCs that overexpress HIF2α and, thus, result in an advanced stage of malignancy Overall, identification of principal up- and down-regulated proteins in the context of specific VHL genotypes would not only enhance the understanding of the major regulators of RCC, but also could potentially streamline strategies to prioritize drug targets for potential therapeutic intervention (Nagaprashantha et al., 2011)