Identification of candidate circulating cisplatin-resistant biomarkers from epithelial ovarian carcinoma cell secretomes

Br J Cancer. 2014 Jan 7;110(1):123-32. doi: 10.1038/bjc.2013.687. Epub 2013 Oct 31.

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.

Conclusion: 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.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Biomarkers, Tumor / biosynthesis
  • Biomarkers, Tumor / blood*
  • Biomarkers, Tumor / genetics
  • Carcinoma, Ovarian Epithelial
  • Cell Line, Tumor
  • Cisplatin / pharmacology
  • Collagen Type XI / biosynthesis
  • Collagen Type XI / blood*
  • Collagen Type XI / genetics
  • Culture Media
  • Disease-Free Survival
  • Drug Resistance, Neoplasm
  • Female
  • Gene Expression
  • Humans
  • Neoplasm Proteins / biosynthesis
  • Neoplasm Proteins / blood*
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism
  • Neoplasms, Glandular and Epithelial / blood*
  • Neoplasms, Glandular and Epithelial / drug therapy
  • Neoplasms, Glandular and Epithelial / genetics
  • Neoplasms, Glandular and Epithelial / metabolism
  • Ovarian Neoplasms / blood*
  • Ovarian Neoplasms / drug therapy
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / metabolism
  • Proteomics
  • Survival Rate

Substances

  • Biomarkers, Tumor
  • COL11A1 protein, human
  • Collagen Type XI
  • Culture Media
  • Neoplasm Proteins
  • Cisplatin