जर्नल ऑफ़ मॉलिक्यूलर बायोमार्कर एंड डायग्नोसिस

Soluble Heparin-Binding EGF-Like Growth Factor (HB-EGF) is a Potential Serological Biomarker for Various Cancer Types

Abstract

Noriyuki Kasai, Yukitaka Yoshikawa, Kazuhiro Kobayashi, Shinobu Shioya, Shingo Miyamoto, Eisuke Mekada and Junichi Enokizono

Background: Heparin-binding EGF-like Growth Factor (HB-EGF), a member of the EGF family, exerts its biological activity through activation of the EGF receptors. HB-EGF is initially synthesized as a membrane-anchored precursor protein (proHB-EGF), and then proteolytically cleaved, resulting in the mitogenically active soluble form. HB-EGF plays pivotal roles in many physiologic and pathologic processes such as development and cell proliferation. In this study, we measured soluble HB-EGF concentrations in serum samples obtained from healthy volunteers and patients of various cancer types.

Materials and methods: Soluble HB-EGF levels in human serum samples were quantified by the immuno-PCR method.

Results: The mean soluble HB-EGF levels of the 20 healthy volunteers and 10 colon, breast, ovarian, head and neck, non-small cell lung, pancreatic, and small cell lung cancer patients were 5.04, 18.0, 15.1, 10.4, 6.69, 9.78, 23.6, and 5.60 pg/mL, respectively. There was a statistically significant difference between the HB-EGF concentrations of healthy volunteers and patients in 5 out of 7 cancer types. Furthermore, a trend for HB-EGF levels to increase along with disease stage was observed.

Conclusion: Soluble HB-EGF may be a useful diagnostic serological biomarker for various cancer types, and a predictive and/or pharmacodynamic biomarker for HB-EGF-targeted therapeutics.