Evaluation of human neutrophil peptide-1, -2 and -3 as serum markers for colorectal cancer

Article type: Research Article

Authors: van den Broek, Irene^{a; *} | Sparidans, Rolf W.^a | Engwegen, Judith Y.M.N^b | Cats, Annemieke^c | Depla, Annekatrien C.T.M.^d | Schellens, Jan H.M.^{a; e} | Beijnen, Jos H.^{a; f}

Affiliations: [a] Utrecht University, Faculty of Science, Department of Pharmaceutical, Sciences, Section of Biomedical Analysis, Division of Drug Toxicology, Utrecht, The Netherlands | [b] Atrium Medical Centre, Department of Pharmacy, Heerlen, The Netherlands | [c] The Netherlands Cancer Institute, Department of Gastroenterology and Hepatology, Amsterdam, The Netherlands | [d] Slotervaart Hospital, Department of Gastroenterology and Hepatology, Amsterdam, The Netherlands | [e] The Netherlands Cancer Institute, Department of Medical Oncology, Division of Clinical Pharmacology, Amsterdam, The Netherlands | [f] Slotervaart Hospital, Department of Pharmacy and Pharmacology, Amsterdam, The Netherlands

Correspondence: [*] Corresponding author: I. van den Broek, 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. Tel.: +31 30 2537377; Fax: +31 30 2535180; E-mail: [email protected].

Abstract: Increased total serum concentrations of human neutrophil peptide-1, -2 and -3 (HNP-1, -2 and -3) have been associated with colorectal cancer (CRC). Owing to a recently developed and fully validated liquid-chromatography coupled to tandem-mass spectrometry (LC-MS/MS) assay, individual serum concentrations of these antimicrobial peptides were quantified to evaluate their role as serum markers in CRC. Serum was obtained from patients with indications for colonoscopy, subsequently diagnosed as normal colon or hyperplastic polyp (CON; n= 368), adenomatous polyp (AP; n = 179) or colorectal cancer (CRC; n = 69). Comparison of HNP-1, -2 and -3 concentrations between CRC and CON (130 ± 90 vs. 105 ± 80; 264 ± 140 vs. 206 ± 99 and 62 ± 56 vs. 54 ± 59 for HNP-1, -2 and -3, respectively) revealed that reported up-regulated total HNP-concentrations can be largely attributed to increased HNP-2 (P=0.0006) and HNP-1 (P=0.024) levels. Although receiver operating characteristics (ROC) analyses showed low specificity of the peptides for CRC and no significant changes in serum levels were observed after surgical removal of the tumor (n=23), the established differentiation between the HNP-subtypes may be particularly useful to completely elucidate the role of these antimicrobial peptides in CRC.

Keywords: Human neutrophil peptides, colorectal cancer, serum markers, LC-MS/MS

DOI: 10.3233/CBM-2010-0153

Journal: Cancer Biomarkers, vol. 7, no. 2, pp. 109-115, 2010