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The absolute quantification of eight inter-α-trypsin inhibitor heavy chain 4 (ITIH4)-derived peptides in serum from breast cancer patients†
Article first published online: 29 NOV 2010
Copyright © 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
PROTEOMICS - Clinical Applications
Special Issue: Focus on Pathways to Translation of Proteomics into Clinical Practice
Volume 4, Issue 12, pages 931–939, December 2010
How to Cite
van den Broek, I., Sparidans, R. W., van Winden, A. W. J., Gast, M.-C. W., van Dulken, E. J., Schellens, J. H. M. and Beijnen, J. H. (2010), The absolute quantification of eight inter-α-trypsin inhibitor heavy chain 4 (ITIH4)-derived peptides in serum from breast cancer patients. Prot. Clin. Appl., 4: 931–939. doi: 10.1002/prca.201000035
- Issue published online: 29 NOV 2010
- Article first published online: 29 NOV 2010
- Accepted manuscript online: 5 OCT 2010 09:01AM EST
- Manuscript Accepted: 23 AUG 2010
- Manuscript Revised: 16 AUG 2010
- Manuscript Received: 5 MAY 2010
- Breast cancer;
Purpose: Various studies exploring the potential of the low-molecular-weight serum peptidome have identified proteolytic cleavage products of inter-α-trypsin inhibitor heavy chain-4 (ITIH4) as potential markers for different types of cancer, presumably generated by tumor-associated exoproteases. However, further elucidation of the discriminative properties of such peptides requires specific quantitative analytical methods.
Experimental design: Using a recently developed and fully validated liquid chromatography–tandem mass spectrometric method, we have compared absolute serum concentrations of eight peptides derived from ITIH4 [658–687] to [667–687] (ITIH4-30 to −21) between breast cancer patients (n=45) and controls (n=78). Furthermore, serum samples obtained before and after surgical removal of the tumor were analyzed (n=30).
Results: The inter-individual variability in measured serum concentrations was high. Nevertheless, most peptides showed a tendency toward elevated levels in the presence of the breast cancer tumor. Significantly increased serum concentrations were observed in the breast cancer group for ITIH4-25 (p=0.036) and −29 (p=0.015). Intra-individual comparisons of serum obtained before and after surgery showed significantly decreased serum levels after surgery for seven of the ITIH4-derived peptides (p<0.02).
Conclusions and clinical relevance: The obtained results particularly suggest potential for these ITIH4-derived peptides in the follow-up of breast cancer after surgery.