Alterations of the serum peptidome in renal cell carcinoma discriminating benign and malignant kidney tumors

• Published in: Journal of proteomics 2012-12, Vol.76, p.125-140
• Main Authors: Gianazza, Erica, Chinello, Clizia, Mainini, Veronica, Cazzaniga, Marta, Squeo, Valeria, Albo, Giancarlo, Signorini, Stefano, Di Pierro, Salvatore S., Ferrero, Stefano, Nicolardi, Simone, van der Burgt, Yuri E.M., Deelder, André M., Magni, Fulvio
• Format: Article
• Language: English
• Subjects: Biological fluids; ClinProt; Magnetic beads; Mass spectrometry; Proteomics
• ISSN: 1874-3919
• DOI: 10.1016/j.jprot.2012.07.032

Renal cell carcinoma (RCC) is typically asymptomatic and surgery usually increases patient's life only for early stage tumors. However, some cystic and solid renal lesions cannot be confidently differentiated from clear-cell-RCC. Therefore possible markers for early detection and to distinguish malignant kidney tumors are needed. To this aim, we applied MALDI-TOF and LC–MS/MS analysis to RPC18 MB purified serum of ccRCC, non-ccRCC patients and controls. A cluster of five signals differentiate malignant tumors from benign renal masses and healthy subjects. Moreover, a combination of six ions showed the highest specificity and sensitivity to distinguish ccRCC from controls. Healthy subjects were also differentiated from non-ccRCC by three features. Peptide ratios obtained by MALDI-TOF were compared with those from label-free LC-ESI and no statistical difference was found (p>0.05). ESI-results were linked with MALDI profiles by both TOF/TOF sequencing and MALDI FT-ICR accurate mass measurements. About 200 unique endogenous peptides, originating from 32 proteins, were identified. Among them, SDPR and ZYX were found down-expressed, while SRGN and TMSL3 were up-expressed. In conclusion, our results suggest the possibility to discriminate malignant kidney tumors based on a cluster of serum peptides. Moreover, label-free approach may represent a valid method to verify results obtained by MALDI-TOF. This article is part of a Special Issue entitled: Integrated omics. [Display omitted] ► Markers for early ccRCC detection and for distinguishing malignant kidney tumors. ► Serum was purified by RPC18 magnetic beads followed by MALDI-TOF and LC–MS/MS. ► Five signals differentiate malignant tumors from benign renal masses and controls. ► No statistical difference between peptide ratios by MALDI and label-free strategy.