Molecular and phenotypic characteristics influencing the degree of cytoreduction in high-grade serous ovarian carcinomas.

Autor: Torkildsen CF; Centre for Cancer Biomarkers, Department of Clinical Science, University of Bergen, Bergen, Norway.; Department of Obstetrics and Gynecology, Stavanger University Hospital, Stavanger, Norway., Thomsen LCV; Centre for Cancer Biomarkers, Department of Clinical Science, University of Bergen, Bergen, Norway.; Department of Obstetrics and Gynecology, Haukeland University Hospital, Bergen, Norway., Sande RK; Department of Obstetrics and Gynecology, Stavanger University Hospital, Stavanger, Norway.; Department of Clinical Science, University of Bergen, Bergen, Norway., Krakstad C; Centre for Cancer Biomarkers, Department of Clinical Science, University of Bergen, Bergen, Norway.; Department of Obstetrics and Gynecology, Haukeland University Hospital, Bergen, Norway., Stefansson I; Centre for Cancer Biomarkers, Department of Clinical Science, University of Bergen, Bergen, Norway.; Department of Pathology, Haukeland University Hospital, Bergen, Norway., Lamark EK; Department of Obstetrics and Gynecology, Haukeland University Hospital, Bergen, Norway., Knappskog S; Department of Clinical Science, University of Bergen, Bergen, Norway.; Department of Oncology, Haukeland University Hospital, Bergen, Norway., Bjørge L; Centre for Cancer Biomarkers, Department of Clinical Science, University of Bergen, Bergen, Norway.; Department of Obstetrics and Gynecology, Haukeland University Hospital, Bergen, Norway.
Jazyk: angličtina
Zdroj: Cancer medicine [Cancer Med] 2023 Jul; Vol. 12 (13), pp. 14183-14195. Date of Electronic Publication: 2023 May 16.
DOI: 10.1002/cam4.6085
Abstrakt: Background: High-grade serous ovarian carcinoma (HGSOC) is the deadliest ovarian cancer subtype, and survival relates to initial cytoreductive surgical treatment. The existing tools for surgical outcome prediction remain inadequate for anticipating the outcomes of the complex relationship between tumour biology, clinical phenotypes, co-morbidity and surgical skills. In this genotype-phenotype association study, we combine phenotypic markers with targeted DNA sequencing to discover novel biomarkers to guide the surgical management of primary HGSOC.
Methods: Primary tumour tissue samples (n = 97) and matched blood from a phenotypically well-characterised treatment-naïve HGSOC patient cohort were analysed by targeted massive parallel DNA sequencing (next generation sequencing [NGS]) of a panel of 360 cancer-related genes. Association analyses were performed on phenotypic traits related to complete cytoreductive surgery, while logistic regression analysis was applied for the predictive model.
Results: The positive influence of complete cytoreductive surgery (R0) on overall survival was confirmed (p = 0.003). Before surgery, low volumes of ascitic fluid, lower CA125 levels, higher platelet counts and relatively lower clinical stage at diagnosis were all indicators, alone and combined, for complete cytoreduction (R0). Mutations in either the chromatin remodelling SWI_SNF (p = 0.036) pathway or the histone H3K4 methylation pathway (p = 0.034) correlated with R0. The R0 group also demonstrated higher tumour mutational burden levels (p = 0.028). A predictive model was developed by combining two phenotypes and the mutational status of five genes and one genetic pathway, enabling the prediction of surgical outcomes in 87.6% of the cases in this cohort.
Conclusion: Inclusion of molecular biomarkers adds value to the pre-operative stratification of HGSOC patients. A potential preoperative risk stratification model combining phenotypic traits and single-gene mutational status is suggested, but the set-up needs to be validated in larger cohorts.
(© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)
Databáze: MEDLINE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje