title: Identification of proteomic and metabolic signatures associated with chemoresistance of human epithelial ovarian cancer.
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.
authors: Department of Gynecologic Oncology, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.
authors: Wenjuan
authors: W
authors: Wu
authors: Key Laboratory of High‑Incidence Tumor Prevention and Treatment (Guangxi Medical University), Ministry of Education, Nanning, Guangxi 530021, P.R. China.
authors: Qi
authors: Q
authors: Wang
authors: Key Laboratory of High‑Incidence Tumor Prevention and Treatment (Guangxi Medical University), Ministry of Education, Nanning, Guangxi 530021, P.R. China.
authors: Fuqiang
authors: F
authors: Yin
authors: Department of Gynecologic Oncology, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.
authors: Zhijun
authors: Z
authors: Yang
authors: Key Laboratory of High‑Incidence Tumor Prevention and Treatment (Guangxi Medical University), Ministry of Education, Nanning, Guangxi 530021, P.R. China.
authors: Wei
authors: W
authors: Zhang
authors: Section of Molecular Therapeutics, Department of Cancer Medicine, Imperial College London, London, UK.
authors: Hani
authors: H
authors: Gabra
authors: Department of Gynecologic Oncology, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.
authors: Li
authors: L
authors: Li
mesh_terms: D002288:Adenocarcinoma, Mucinous / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism; D015153:Blotting, Western; D002853:Chromatography, Liquid; D019295:Computational Biology; D018284:Cystadenocarcinoma, Serous / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D019008:Drug Resistance, Neoplasm; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D055432:Metabolomics / Q000379:methods*; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D040901:Proteomics / Q000379:methods*; D015398:Signal Transduction / Q000187:drug effects; D053719:Tandem Mass Spectrometry; D014407:Tumor Cells, Cultured
chemical_list: D014408:Biomarkers, Tumor