Nectin-4 as Blood-Based Biomarker Enables Detection of Early Ovarian Cancer Stages

SIMPLE SUMMARY: Ovarian cancer is usually diagnosed in an advanced stage of the disease and is associated with a poor prognosis. Therefore, it is important to find reliable biomarkers that allow early diagnosis. In this study, we detected elevated Nectin-4 and HB-EGF serum levels in ovarian cancer patients which correlate with prognostically favorable parameters, such as early FIGO stage and successful tumor debulking. In addition, Nectin-4 was elevated in patients with low blood levels of Ca-125. This suggests that Nectin-4 and Ca-125 provide complementary diagnostic information. Therefore, Nectin-4 and HB-EGF appear to be promising blood-based biomarkers for the diagnosis of early stages of ovarian cancer. ABSTRACT: Ovarian cancer is the third most common gynecological malignancy and has the highest mortality rate. Owing to unspecific symptoms, ovarian cancer is not detected until an advanced stage in about two-thirds of cases. Therefore, it is crucial to establish reliable biomarkers for the early stages to improve the patients’ prognosis. The aim of this study is to investigate whether the ADAM17 substrates Nectin-4, Heparin-binding EGF-like growth factor (HB-EGF) and Amphiregulin (AREG) could function as potential tumor markers for ovarian cancer. In this study a set of 231 sera consisting of 131 ovarian cancer patients and 100 healthy age-matched controls were assembled. Nectin-4, HB-EGF and AREG levels of preoperatively collected sera were determined by enzyme-linked immunosorbent assay (ELISA). Our analysis revealed that Nectin-4 and HB-EGF were significantly increased compared to the age-matched control group (p < 0.0001, p = 0.016). Strikingly, significantly higher Nectin-4 and HB-EGF levels were detected in early-stage FIGO I/II (p <0.001; p = 0.025) compared to healthy controls. Eighty-four percent (16/19) of patients with low Ca-125 levels showed increased Nectin-4 levels. Our study proposes Nectin-4 and HB-EGF as promising blood-based biomarkers for the detection of early stages of ovarian cancer patients that would not have been detected by Ca-125.