Serum Comparative Proteomics And Metabolomics Study On The MDR Epithelial Ovarian Neoplasms

Objective To explore serum biomarkers and the molecular mechanism associated withmultidrug resistance(MDR) of epithelial ovarian cancer(EOC), Proteomics and Metabolomicsapproach were used to examine the differentially express level of proteins and metaboliccompounds in EOC patients, leading to found the therapy target which can reverse the MDR.Methods Patients with pathologically confirmed EOC platinum-sensitive (PTS), EOCplatinum-resistant (PTR), benign ovarian cyst(BOC) and normal health individuals wereeligible. Differentially express level of proteins were identified with Isobaric tags for relativeand absolute quantitation (iTRAQ) based quantitative proteomic approach and then weresubjected to bioinformatics analysis. Proteins that played a important role in MDR werevalidated by enzyme-linked immunosorbent assay (ELISA) and Western blot (WB).Meanwhile, Liquid chromatography-mass spectrometry in positive ion mode were used todetect the serum metabolic finger printing in132cases of above four groups.Results More than three hundred proteins from two independently studies were identified.Four groups were compared pairwise, especially the PTS and PTR.64proteins were screenedout as candidate biomarkers between PTS and PTR and then subjected to bioinformaticsanalysis. On the other hand,25580metabolic compounds were identified, according to theresults of principal component analysis,6of them are the biggest contributor to the group andclosely with clinical characteristics.Conclusion The differentially express level of SERPINA1、FN1GPX3and the six metabolic compounds between PTS and PTR play a essential role in measuring subtle changes inresponse to platinum-based chemotherapy and may be involved in biological processes ofMDR. Our findings may provide some promising candidate biomarkers for platinum status,even lead to novel target for reversing MDR.