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

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Title: Identification of proteomic and metabolic signatures associated with chemoresistance of human epithelial ovarian cancer
Author(s): Wu, W
Wang, Q
Yin, F
Yang, Z
Zhang, W
Gabra, H
Li, L
Item Type: Journal Article
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.
Publication Date: 10-Aug-2016
Date of Acceptance: 10-Aug-2016
URI: http://hdl.handle.net/10044/1/44224
DOI: https://dx.doi.org/10.3892/ijo.2016.3652
ISSN: 1791-2423
Publisher: Spandidos Publications
Start Page: 1651
End Page: 1665
Journal / Book Title: International Journal of Oncology
Volume: 49
Issue: 4
Copyright Statement: © Spandidos Publications 2016. All rights reserved.
Keywords: Science & Technology
Life Sciences & Biomedicine
Oncology
ovarian cancer
drug resistance
isobaric tags for relative and absolute quantitation
proteomics
metabolomics
GLUTATHIONE-PEROXIDASE 3
FATTY-ACID SYNTHASE
HUMAN ALPHA-1-ACID GLYCOPROTEIN
ACUTE-PHASE PROTEIN
ALPHA(1)-ACID GLYCOPROTEIN
DRUG-RESISTANCE
BREAST-CANCER
GENE-EXPRESSION
FIBRONECTIN 1
CELLS
Oncology & Carcinogenesis
1112 Oncology And Carcinogenesis
Publication Status: Published
Appears in Collections:Division of Cancer
Faculty of Medicine



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