Abstract
Simple SummaryOvarian cancer has the highest lethality among gynecological tumors. Therefore, it is essential to find reliable biomarkers to improve early detection. This is the first report describing ADAM17 detection in serum and ascites fluid of ovarian cancer patients. A high ADAM17 concentration in serum at primary diagnosis is associated with early FIGO stages and predicts complete resection of the tumor mass. In addition, ADAM17 and CA-125 complement each other, especially in the diagnosis of early stages. In summary, ADAM17 appears to be a promising screening marker for detecting early-stage ovarian cancer.Ovarian cancer has the highest mortality rate among gynecological tumors. This is based on late diagnosis and the lack of early symptoms. To improve early detection, it is essential to find reliable biomarkers. The metalloprotease ADAM17 could be a potential marker, as it is highly expressed in many solid tumors, including ovarian and breast cancer. The aim of this work is to evaluate the relevance of ADAM17 as a potential diagnostic blood-based biomarker in ovarian cancer. Ovarian cancer cell lines IGROV-1 and A2780, as well as primary patient-derived tumor cells obtained from tumor tissue and ascitic fluid, were cultured to analyze ADAM17 abundance in the culture supernatant. In a translational approach, a cohort of 117 well-characterized ovarian cancer patients was assembled and ADAM17 levels in serum and corresponding ascitic fluid were determined at primary diagnosis. ADAM17 was quantified by enzyme-linked immunosorbent assay (ELISA). In the present study, ADAM17 was detected in the culture supernatant of ovarian cancer cell lines and primary cells. In addition, ADAM17 was found in serum and ascites of ovarian cancer patients. ADAM17 level was significantly increased in ovarian cancer patients compared to an age-matched control group (p < 0.0001). Importantly early FIGO I/II stages, which would not have been detected by CA-125, were associated with higher ADAM17 concentrations (p = 0.007). This is the first study proposing ADAM17 as a serum tumor marker in the setting of a gynecological tumor disease. Usage of ADAM17 in combination with CA-125 and other markers could help detect early stages of ovarian cancer.
Highlights
With more than 100,000 deaths per year worldwide, ovarian cancer is the most lethal cancer amongst all gynecological malignancies [1]
We have recently shown that the a disintegrin and metalloprotease 17 (ADAM17) protein is expressed by ascites derived from ovarian cancer cells [15]
The ovarian cancer cell line A2780 was purchased from Sigma-Aldrich and the human ovarian adenocarcinoma cell line IGROV-1 was obtained from American Type Culture Collection (ATCC)
Summary
With more than 100,000 deaths per year worldwide, ovarian cancer is the most lethal cancer amongst all gynecological malignancies [1]. The second challenge in ovarian cancer is the resistance to chemotherapeutic treatment, which often leads to recurrent disease [3]. Treatment of advanced ovarian cancer is challenging because tumor-free resection (R0-surgery) is less likely, as the tumor has already spread widely in the peritoneal cavity. Because tumor-free resection, ever since, has led to better survival rates, it is of major clinical importance to find novel biomarkers indicating malignant changes of the ovaries in early stages [4]. Most tumor markers in the early stages show low sensitivity (stage I 40–50%) [5]. Benign diseases such as endometriosis can lead to increased levels of cancer antigen 125 (CA-125), which significantly limits specificity [6]
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