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.