Identification of proteomic and metabolic signatures associated with chemoresistance of human epithelial ovarian cancer

Abstract

Abstract. Emerging drug resistance in epithelial ovarian cancer (EOC) thwarted progress in platinum-based chemotherapy, resulting in increased mortality, morbidity and healthcare costs. The aim of this study was to detect the responses induced by chemotherapy at protein and metabolite levels, and to search for new plasma markers that can predict resistance to platinum-based chemotherapy in EOC patients, leading to improved clinical response rates. Serum samples were collected and subjected to proteomic relative quantitation analysis and metabolomic analysis. Differentially expressed proteins and metabolites were subjected to bioinformatics and statistical analysis. Proteins that played a key role in platinum resistance were validated by western blotting and enzyme-linked immunosorbent assay (ELISA). Metabolites that were the main contributors to the groups and closely with clinical characteristics were identified based on the database using nuclear magnetic resonance (NMR). In total, 248 proteins from two independent experiments were identified using isobaric tags for relative and absolute quantitation (iTRAQ)-based quantitative proteomic approach. Among them, FN1, SERPINA1, GPX3 and ORM1 were chosen for western blotting and ELISA validation. Platinum resistance likely associated with differentially expressed proteins and FN1, SERPINA1 and ORM1 may play a positive role in chemotherapy. HPLC-MS analysis of four groups revealed a total of 25,800 metabolic features, of which six compounds were chosen for candidate biomarkers and identified based on the database using NMR. The metabolic signatures of normal control (NC), platinum-sensitive (PTS) and platinum-resistant (PTR) groups were clearly separated from each other.Those findings may provide theoretical clues for the prediction of chemotherapeutic response and reverse of drug resistance, even lead to novel targets for therapeutic intervention.

Dietary Selenium Supplementation Ameliorates Female Reproductive Efficiency in Aging Mice

“…Available evidence highlights that studies focusing on role of Se as an essential trace element in female reproduction are mainly focused on human pregnancy [30] and related complications such as pre-eclampsia [31], miscarriage and preterm birth [9,32], intrauterine growth restriction [33], small-for-gestational age newborns [34], pregnancy-induced hypertension [35], and pregnancy-related autoimmune thyroid disease [36]. Lower Se status and glutathione peroxidase 3 (GPX3) activity are shown to contribute in the progression of neoplastic diseases of female reproductive system including endometrial and ovarian cancers [37][38][39][40]. In addition, a few recent reports have also demonstrated that Se deficiency was linked to the contractile dysfunction of uterine smooth muscles in young mice [41][42][43].…”

The role of ROS and subsequent DNA-damage response in PUMA-induced apoptosis of ovarian cancer cells

“…Although treatment with platinum and paclitaxel can prolong survival to some extent, drug resistance often leads to therapy failure [4, 5]. Nevertheless, some novel molecular targets have been discovered for treating ovarian cancer [6–9]. …”

STROBE-compliant integrin through focal adhesion involve in cancer stem cell and multidrug resistance of ovarian cancer

“…In the preliminary work of this study, we are using proteomics and metabolomics screening multiple genes associated with ovarian cancer drug resistance [44] ; among them, fibronectin 1(FN1) and integrin coincide with the results of this study; therefore, we choose integrins for further research.…”