title: Identification of candidate circulating cisplatin-resistant biomarkers from epithelial ovarian carcinoma cell secretomes.
abstract: BACKGROUND
  The majority of patients diagnosed with advanced epithelial ovarian carcinoma (EOC) relapse with resistant disease, and there are no biomarkers that possess clinical utility to identify or monitor these patients. This study aimed to identify secreted proteins ('secretome') collected from human EOC cell lines that differ in their inherent platinum sensitivity.
  
  
  METHODS
  Secreted proteins collected from conditioned medium from ovarian cancer cell lines that vary in their sensitivity to cisplatin were digested with trypsin and analysed by liquid chromatography-tandem mass spectrometry for peptide identification.
  
  
  RESULTS
  Of the 1688 proteins identified, 16 possessed significant differential abundances (P<0.05) between the platinum-resistant and -sensitive cell lines. A number of these were verified by immunoblot, including COL11A1, which was also found to be associated with worse progression-free survival (PFS; N=723) and overall survival (OS; N=1183) as assessed from publicly available transcript expression data from ovarian cancer tumour specimens.
  
  
  CONCLUSIONS
  Secretome proteomics of EOC cells resulted in the identification of a novel candidate biomarker, COL11A1. The expression level of COL11A1 correlates to worse PFS and OS, and is predicted to reside in peripheral circulation making this an attractive candidate for validation in sera as a biomarker of cisplatin resistance and poor outcome.
authors.affiliation: Women's Health Integrated Research Center at Inova Health System, Gynecologic Cancer Center of Excellence, 3289 Woodburn Road, Suite 370, Annandale, VA 22003, USA.
authors.forename: P-N
authors.initials: PN
authors.lastname: Teng
authors.affiliation: Women's Health Integrated Research Center at Inova Health System, Gynecologic Cancer Center of Excellence, 3289 Woodburn Road, Suite 370, Annandale, VA 22003, USA.
authors.forename: G
authors.initials: G
authors.lastname: Wang
authors.affiliation: Women's Health Integrated Research Center at Inova Health System, Gynecologic Cancer Center of Excellence, 3289 Woodburn Road, Suite 370, Annandale, VA 22003, USA.
authors.forename: B L
authors.initials: BL
authors.lastname: Hood
authors.affiliation: Women's Health Integrated Research Center at Inova Health System, Gynecologic Cancer Center of Excellence, 3289 Woodburn Road, Suite 370, Annandale, VA 22003, USA.
authors.forename: K A
authors.initials: KA
authors.lastname: Conrads
authors.affiliation: 1] Women's Health Integrated Research Center at Inova Health System, Gynecologic Cancer Center of Excellence, 3289 Woodburn Road, Suite 370, Annandale, VA 22003, USA [2] Gynecologic Oncology Service, Department of Obstetrics and Gynecology, Walter Reed National Military Medical Center, 8901 Wisconsin Avenue, Bethesda, MD 20814, USA.
authors.forename: C A
authors.initials: CA
authors.lastname: Hamilton
authors.affiliation: 1] Women's Health Integrated Research Center at Inova Health System, Gynecologic Cancer Center of Excellence, 3289 Woodburn Road, Suite 370, Annandale, VA 22003, USA [2] Department of Obstetrics and Gynecology, Inova Fairfax Hospital, 3300 Gallows Road, Falls Church, VA 22042, USA.
authors.forename: G L
authors.initials: GL
authors.lastname: Maxwell
authors.affiliation: Women's Health Integrated Research Center at Inova Health System, Gynecologic Cancer Center of Excellence, 3289 Woodburn Road, Suite 370, Annandale, VA 22003, USA.
authors.forename: K M
authors.initials: KM
authors.lastname: Darcy
authors.affiliation: Women's Health Integrated Research Center at Inova Health System, Gynecologic Cancer Center of Excellence, 3289 Woodburn Road, Suite 370, Annandale, VA 22003, USA.
authors.forename: T P
authors.initials: TP
authors.lastname: Conrads
mesh_terms: D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000097:blood* / Q000235:genetics; D000077216:Carcinoma, Ovarian Epithelial; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology; D024161:Collagen Type XI / Q000096:biosynthesis / Q000097:blood* / Q000235:genetics; D003470:Culture Media; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm; D005260:Female; D015870:Gene Expression; D006801:Humans; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000097:blood* / Q000235:genetics / Q000378:metabolism; D009375:Neoplasms, Glandular and Epithelial / Q000097:blood* / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000097:blood* / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D040901:Proteomics; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; C574182:COL11A1 protein, human; D024161:Collagen Type XI; D003470:Culture Media; D009363:Neoplasm Proteins; D002945:Cisplatin