Predictive biomarker for surgical outcome in patients with advanced primary high-grade serous ovarian cancer. Are we there yet? An analysis of the prospective biobank for ovarian cancer

• Published in: Gynecologic oncology 2022-08, Vol.166 (2), p.334-343
• Main Authors: Keunecke, Carlotta, Kulbe, Hagen, Dreher, Felix, Taube, Eliane T., Chekerov, Radoslav, Horst, David, Hummel, Michael, Kessler, Thomas, Pietzner, Klaus, Kassuhn, Wanja, Heitz, Florian, Muallem, Mustafa Z., Lang, Susan M., Vergote, Ignace, Dorigo, Oliver, Lammert, Hedwig, du Bois, Andreas, Angelotti, Tim, Fotopoulou, Christina, Sehouli, Jalid, Braicu, Elena I.
• Format: Article
• Language: English
• Subjects: High-grade serous ovarian cancer; Nanostring; Predictive biomarker; Primary debulking
• ISSN: 0090-8258; 1095-6859
• DOI: 10.1016/j.ygyno.2022.06.010

High-grade serous ovarian cancer (HGSOC) is the most common subtype of ovarian cancer and is associated with high mortality rates. Surgical outcome is one of the most important prognostic factors. There are no valid biomarkers to identify which patients may benefit from a primary debulking approach. Our study aimed to discover and validate a predictive panel for surgical outcome of residual tumor mass after first-line debulking surgery. Firstly, “In silico” analysis of publicly available datasets identified 200 genes as predictors for surgical outcome. The top selected genes were then validated using the novel Nanostring method, which was applied for the first time for this particular research objective. 225 primary ovarian cancer patients with well annotated clinical data and a complete debulking rate of 60% were compiled for a clinical cohort. The 14 best rated genes were then validated through the cohort, using immunohistochemistry testing. Lastly, we used our biomarker expression data to predict the presence of miliary carcinomatosis patterns. The Nanostring analysis identified 37 genes differentially expressed between optimal and suboptimal debulked patients (p < 0.05). The immunohistochemistry validated the top 14 genes, reaching an AUC Ø0.650. The analysis for the prediction of miliary carcinomatosis patterns reached an AUC of Ø0.797. The tissue-based biomarkers in our analysis could not reliably predict post-operative residual tumor. Patient and non-patient-associated co-factors, surgical skills, and center experience remain the main determining factors when considering the surgical outcome at primary debulking in high-grade serous ovarian cancer patients. •Predictive tools for the surgical outcome of patients with ovarian cancer are needed.•To establish predictive tools a large and defined patient cohort is needed.•Techniques like Nanostring and Immunohistochemistry can be used to select biomarkers.•A predictive gene panel using Nanostring technique was tried but was not successful.•A gene signature for diffuse peritoneal carcinomatosis could be described.