title: Soluble heparin-binding EGF-like growth factor (HB-EGF) detected by newly developed immuno-PCR method is a clear-cut serological biomarker for ovarian cancer.
abstract: Heparin-binding EGF-like growth factor (HB-EGF) is a member of the EGF family of growth factors that bind to and activate the EGF receptor. HB-EGF is synthesized as a membrane-anchored protein (proHB-EGF), and then proteolytically cleaved, resulting in the mitogenically active soluble form. HB-EGF plays pivotal roles in pathophysiological processes such as development and cell proliferation. In this study, we developed an immuno-PCR system for the determination of soluble HB-EGF concentrations in human serum. Utilizing a monoclonal antibody with neutralizing activity against HB-EGF as a capture antibody resulted in increasing selectivity for an active form of HB-EGF in serum, and immuno-PCR system improved its sensitivity compared to the currently available methods. As a result of measurement of HB-EGF in 20 ovarian cancer patients and 20 healthy volunteers, ovarian cancer patients showed significantly higher concentrations than healthy volunteers (P< 0.05), which indicates that soluble HB-EGF detected by newly developed immuno-PCR system can be useful serological biomarkers such as a diagnostic biomarker for ovarian cancer, and a predictive and pharmacodynamic biomarker for anti-HB-EGF targeted therapies under development.
authors.affiliation: Pharmacokinetic Research Laboratories, Kyowa Hakko Kirin Co. Ltd. 1188, Shimotogari, Nagaizumi-cho, Suntogun, Shizuoka, 411-8731, Japan.
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Kasai
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Kobayashi
authors.forename: Shinobu
authors.initials: S
authors.lastname: Shioya
authors.forename: Yukitaka
authors.initials: Y
authors.lastname: Yoshikawa
authors.forename: Fusanori
authors.initials: F
authors.lastname: Yotsumoto
authors.forename: Shingo
authors.initials: S
authors.lastname: Miyamoto
authors.forename: Eisuke
authors.initials: E
authors.lastname: Mekada
authors.forename: Junichi
authors.initials: J
authors.lastname: Enokizono
keywords: HB-EGF; immuno-PCR; ovarian cancer; serological biomarker