4.5 Article

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

Journal

JOURNAL OF PROTEOMICS
Volume 76, Issue -, Pages 125-140

Publisher

ELSEVIER
DOI: 10.1016/j.jprot.2012.07.032

Keywords

ClinProt; Biological fluids; Proteomics; Magnetic beads; Mass spectrometry

Funding

  1. Italian Ministry of University and Research: PRIN [69373]
  2. Italian Ministry of University and Research: FIRB (Rete nazionale per lo studio del proteoma umano) [RBRN07BMCT_11]
  3. Italian Ministry of University and Research: FAR
  4. Italian Institute of Technology (IIT)
  5. FONDO PER LA PROMOZIONE DI ACCORDI ISTITUZIONALI Regione Lombardia DGR [5200/2007]
  6. Network Enabled Drug Design (NEDD) [14546]
  7. EuroKUP COST Action [BM0702]

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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. (C) 2012 Elsevier B.V. All rights reserved.

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