P135 Discovery and validation of novel biomarkers for detection of epithelial ovarian cancer. (1st November 2019) - Kulbe, H
Abstract : Introduction/Background: Early detection of epithelial ovarian cancer (EOC) is poses a critical medical challenge, however, novel biomarkers for early diagnosis remain to be discovered. Here, we investigate both epithelial and stromal compartments, which have been neglected in the past in search for novel candidates. Methodology: We queried gene expression profiles of microdissected epithelium and adjacent stroma from benign and malignant tumors (GSE29156) and normal epithelium samples (GSE14407). Genes significantly differentially expressed within either the epithelial or specifically the stromal compartments were retrieved. The expression of genes whose products are secreted yet absent in the blood of healthy donors were validated in tissue and blood from patients with pelvic mass by NanoString analysis. Results were confirmed by the independent gene expression database CSIOVDB. Results: Top 25% of candidate genes were validated, twelve were able to discriminate between benign and malignant tumors on transcript levels (p<0.05). The stroma-derived candidates versican (VCAN) and syndecan-3 (SDC3) were increased in blood of patients with EOC ovarian cancer compared with benign gynecological conditions. Transcript levels of the nuclear orphan receptor NR2F6, denticleless E3 ubiquitin protein ligase DTL, myelin and lymphocyte protein MAL, aurora kinase A (AURKA), VCAN and SDC3 genes performed significantly better than those of known biomarkers to discern malignant from benign conditions. Furthermore, elevated MAL and AURKA expression levels correlated significantly with poor prognosis. Conclusion: We identified promising novel candidates and found the stroma of ovarian cancer to be a suitable compartment for early detection biomarker discovery. Disclosure: Nothing to disclose.