Get access

The absolute quantification of eight inter-α-trypsin inhibitor heavy chain 4 (ITIH4)-derived peptides in serum from breast cancer patients

Authors

  • Irene van den Broek,

    Corresponding author
    1. Utrecht University, Faculty of Science, Department of Pharmaceutical Sciences, Section of Biomedical Analysis, Division of Drug Toxicology, Utrecht, The Netherlands
    • Utrecht University, Faculty of Science, Department of Pharmaceutical Sciences, Section of Biomedical Analysis, Division of Drug Toxicology, Sorbonnelaan 16, room N-715, 3584 CA Utrecht, The Netherlands Fax: +31-30-2535180
    Search for more papers by this author
  • Rolf W. Sparidans,

    1. Utrecht University, Faculty of Science, Department of Pharmaceutical Sciences, Section of Biomedical Analysis, Division of Drug Toxicology, Utrecht, The Netherlands
    Search for more papers by this author
  • Annemieke W. J. van Winden,

    1. Slotervaart Hospital, Department of Pharmacy and Pharmacology, Amsterdam, The Netherlands
    2. Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands
    Search for more papers by this author
  • Marie-Christine W. Gast,

    1. Slotervaart Hospital, Department of Pharmacy and Pharmacology, Amsterdam, The Netherlands
    Search for more papers by this author
  • Eric J. van Dulken,

    1. Slotervaart Hospital, Department of Surgery, Amsterdam, The Netherlands
    Search for more papers by this author
  • Jan H. M. Schellens,

    1. Utrecht University, Faculty of Science, Department of Pharmaceutical Sciences, Section of Biomedical Analysis, Division of Drug Toxicology, Utrecht, The Netherlands
    2. The Netherlands Cancer Institute, Department of Clinical Pharmacology, Amsterdam, The Netherlands
    Search for more papers by this author
  • Jos H. Beijnen

    1. Utrecht University, Faculty of Science, Department of Pharmaceutical Sciences, Section of Biomedical Analysis, Division of Drug Toxicology, Utrecht, The Netherlands
    2. Slotervaart Hospital, Department of Pharmacy and Pharmacology, Amsterdam, The Netherlands
    Search for more papers by this author

  • Colour Online: See the article online to view Fig. 1 in colour.

Abstract

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.

Ancillary