Ivan Verdenik

Bisphenol A in the Urine: Association with Urinary Creatinine, Impaired Kidney Function, Use of Plastic Food and Beverage Storage Products but Not with Serum Anti-Müllerian Hormone in Ovarian Malignancies

Bisphenol A (BPA) is a high-production-volume industrial chemical and component of commonly used plastic products. However, it is also an endocrine-disrupting chemical that can negatively affect human health. It is not yet known whether it is associated with the development of epithelial ovarian cancer (EOC), a severe and highly fatal human disease. Therefore, the purpose of this study was to determine the concentrations of BPA in the urine of women with EOC or epithelial borderline ovarian tumors (EBOTs) using gas chromatography tandem mass spectrometry (GC-MS/MS) and find their possible associations with kidney function at the molecular level, urine and blood biochemical parameters related to metabolism, anti-Müllerian hormone (AMH) (a marker of ovarian reserve/fertility), and lifestyle habits determined via a questionnaire in comparison to healthy controls. The results suggest that the unadjusted or urine-specific-gravity-adjusted BPA levels were significantly increased in women with EOC/EBOT. The unadjusted BPA was significantly positively associated with urinary creatinine (p = 0.007) in all women with EOC/EBOT after adjustment for age, body mass index, and pregnancy using multiple linear regression analysis. This may be related to kidney injury. However, no association was found between urinary BPA and serum AMH levels in women. Women with ovarian malignancies were more exposed to plastic products for storing foods and drinks. Some lifestyle habits, including refilling plastic bottles, correlate with higher urinary BPA levels across the entire cohort of women. When considering EOC or EBOT, it is necessary to consider the potential higher exposure of women to BPA, as reflected in their urine and lifestyle habits.

Higher EpCAM-Positive Extracellular Vesicle Concentration in Ascites Is Associated with Shorter Progression-Free Survival of Patients with Advanced High-Grade Serous Carcinoma

Platinum-resistant high-grade serous carcinoma (HGSC) is an incurable disease, so biomarkers that could help with timely treatment adjustments and personalized approach are extensively being sought. Tumor-derived extracellular vesicles (EVs) that can be isolated from ascites and blood of HGSC patients are such promising biomarkers. Epithelial cell adhesion molecule (EpCAM) expression is upregulated in most epithelium-derived tumors; however, studies on prognostic value of EpCAM overexpression in ovarian carcinoma have shown contradictory results. The aim of our study was to evaluate the potential of total and EpCAM-positive EVs as prognostic and predictive biomarkers for advanced HGSC. Flow cytometry was used to determine the concentration of total and EpCAM-positive EVs in paired pretreatment ascites and plasma samples of 37 patients with advanced HGSC who underwent different first-line therapy. We found that higher EpCAM-positive EVs concentration in ascites is associated with shorter progression-free survival (PFS) regardless of treatment strategy. We also found a strong correlation of EpCAM-positive EVs concentration between ascites and plasma. Our findings indicate that EpCAM-positive EVs in ascites of patients with advanced HGSC have the potential to serve as prognostic biomarkers for predicting early recurrence and thereby likelihood of more aggressive tumor biology and development of chemoresistance.