title: Proteomics Analysis of Ovarian Cancer Cell Lines and Tissues Reveals Drug Resistance-associated Proteins.
abstract: Carboplatin and paclitaxel form the cornerstone of chemotherapy for epithelial ovarian cancer, however, drug resistance to these agents continues to present challenges. Despite extensive research, the mechanisms underlying this resistance remain unclear.
  
  
  
  A 2D-gel proteomics method was used to analyze protein expression levels of three human ovarian cancer cell lines and five biopsy samples. Representative proteins identified were validated via western immunoblotting. Ingenuity pathway analysis revealed metabolomic pathway changes.
  
  
  
  A total of 189 proteins were identified with restricted criteria. Combined treatment targeting the proteasome-ubiquitin pathway resulted in re-sensitisation of drug-resistant cells. In addition, examination of five surgical biopsies of ovarian tissues revealed α-enolase (ENOA), elongation factor Tu, mitochondrial (EFTU), glyceraldehyde-3-phosphate dehydrogenase (G3P), stress-70 protein, mitochondrial (GRP75), apolipoprotein A-1 (APOA1), peroxiredoxin (PRDX2) and annexin A (ANXA) as candidate biomarkers of drug-resistant disease.
  
  
  
  Proteomics combined with pathway analysis provided information for an effective combined treatment approach overcoming drug resistance. Analysis of cell lines and tissues revealed potential prognostic biomarkers for ovarian cancer.
authors.affiliation: Department of Pharmaceutical & Biological Chemistry, UCL School of Pharmacy, London, U.K.
authors.forename: Isa N
authors.initials: IN
authors.lastname: Cruz
authors.affiliation: Faculty of Health and Medical Sciences, University of Surrey, Guildford, Surrey, U.K.
authors.forename: Helen M
authors.initials: HM
authors.lastname: Coley
authors.affiliation: Department of Physiology, Anatomy and Genetic, University of Oxford, South Parks Road, Oxford, U.K.
authors.forename: Holger B
authors.initials: HB
authors.lastname: Kramer
authors.affiliation: Faculty of Health and Medical Sciences, University of Surrey, Guildford, Surrey, U.K.|Section of Gynaecological Oncology, Royal Surrey County Hospital, Guildford, Surrey, U.K.
authors.forename: Thumuluru Kavitah
authors.initials: TK
authors.lastname: Madhuri
authors.affiliation: Faculty of Health and Medical Sciences, University of Surrey, Guildford, Surrey, U.K.
authors.forename: Nur A M
authors.initials: NA
authors.lastname: Safuwan
authors.affiliation: Department of Pharmaceutical & Biological Chemistry, UCL School of Pharmacy, London, U.K.
authors.forename: Ana Rita
authors.initials: AR
authors.lastname: Angelino
authors.affiliation: Department of Pharmaceutical & Biological Chemistry, UCL School of Pharmacy, London, U.K. min.yang@ucl.ac.uk.
authors.forename: Min
authors.initials: M
authors.lastname: Yang
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D015415:Biomarkers; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003131:Combined Modality Therapy; D019295:Computational Biology / Q000379:methods; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D025941:Protein Interaction Mapping; D020543:Proteome; D040901:Proteomics / Q000379:methods; D015398:Signal Transduction; D054875:Ubiquitination
chemical_list: D000970:Antineoplastic Agents; D015415:Biomarkers; D020543:Proteome
keywords: 2D-gel proteomics; Ovarian cancer; biomarker; drug resistance targets; tissue biopsies