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

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 (ITIH(4)) 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 ITIH(4 [658-687]) to ([667-687]) (ITIH(4)-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 ITIH(4)-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 ITIH(4)-derived peptides (p<0.02).

Conclusions and clinical relevance: The obtained results particularly suggest potential for these ITIH(4)-derived peptides in the follow-up of breast cancer after surgery.