Geburtshilfe Frauenheilkd 2016; 76 - FV007
DOI: 10.1055/s-0036-1593244

High-grade serous ovarian and peritoneal cancers display distinct genetic and post-translational signatures – a criterion to treat them differently?

F Jacob 1, 2, M Anugraham 3, A Schötzau 2, A Everest-Dass 3, N Bovin 4, M Huflejt 5, A Fedier 2, N Hacker 6, D Fink 7, N Packer 3, V Heinzelmann-Schwarz 2, 8, 9
  • 1University Hospital Basel, University of Basel, Glyco-Oncology Group, Ovarian Cancer Research, Department of Biomedicine, Basel, Schweiz
  • 2University Hospital Basel, University of Basel, Ovarian Cancer Research, Department of Biomedicine, Basel, Schweiz
  • 3Faculty of Science, Macquarie University, Department of Chemistry & Biomolecular Sciences, Biomolecular Frontiers Research Centre, Sydney, Australien
  • 4Russian Academy of Sciences, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Moscow, Russische Föderation
  • 5New York University School of Medicine, Department of Cardiothoracic Surgery, Division of Thoracic Surgery and Thoracic Oncology, New York, Vereinigte Staaten von Amerika
  • 6University of New South Wales, Royal Hospital for Women, Gynecological Cancer Centre, School of Women's and Children's Health, Sydney, Australien
  • 7University Hospital Zurich, Department of Gynecology, Zurich, Schweiz
  • 8University Hospital Basel, University of Basel, Hospital for Women, Department of Gynecology and Gynecological Oncology, Basel, Schweiz
  • 9University of New South Wales, Prince of Wales Clinical School, Adult Cancer Program, Lowy Cancer Research Centre, Sydney, Australien

Introduction and aim: High-grade serous ovarian (HGSOC), tubal, and peritoneal adenocarcinomas (HGSPC), commonly presenting at an advanced stage and being associated with high mortality rates, are currently treated the same way. We hypothesize that HGSOC and HGSPC are distinguishable by their genetic and molecular profiles and hence are different diseases.

Material and methods: Two independent cohorts (560 patients) were reviewed regarding relapse- and disease-free survival in HGSOC and HGSPC; differential gene expression was determined by Tothill data analysis; differential glycoprotein and post-translational glycan signatures were determined in cancer tissues (mass spectrometry) and in blood plasma (printed glycan array).

Results: HGSPC patients relapse and decease earlier than HGSOC patients, indicating that HGSPC is more aggressive. HGSPC and HGSOC are distinguishable with high discriminatory power (1) on the gene expression level, with alcohol dehydrogenase 1B (ADH1B) being to top single-gene discriminator, and even better with a set of 40 differentially expressed genes; (2) on the level of blood-derived anti-glycan antibodies against specific glycans printed on the array; and (3) on the basis of distinct profiles of N- and O-glycans attached to glycoproteins of cancer cells. In the latter context, unique N-linked structure LacdiNAc on glycoproteins was detected preferentially in HGSOC tissues.

Conclusion: HGSOC and HGSPC cells display distinct molecular signatures on the genetic, post-translational, and anti-glycan antibody levels, and therefore should be considered two different diseases and treated individually according to their profiles. The distinction by the antibodies may serve diagnostic purposes and the LacdiNAc-structure as ideal candidate for targeted HGSOC therapies.