Primary Treatment Effects for High-Grade Serous Ovarian Carcinoma Evaluated by Changes in Serum Metabolites and Lipoproteins
Cecilie Fredvik Torkildsen,
Marie Austdal,
Ann-Charlotte Iversen,
Tone Frost Bathen,
Guro Fanneløb Giskeødegård,
Elisabeth Berge Nilsen,
Grete Alræk Iversen,
Ragnar Kvie Sande,
Line Bjørge,
Liv Cecilie Vestrheim Thomsen
Affiliations
Cecilie Fredvik Torkildsen
Department of Obstetrics and Gynecology, Stavanger University Hospital, 4068 Stavanger, Norway
Marie Austdal
Department of Research, Stavanger University Hospital, 4068 Stavanger, Norway
Ann-Charlotte Iversen
Centre of Molecular Inflammation Research (CEMIR), Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology (NTNU), 7491 Trondheim, Norway
Tone Frost Bathen
Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, 7491 Trondheim, Norway
Guro Fanneløb Giskeødegård
K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, Norwegian University of Science and Technology (NTNU), 7491 Trondheim, Norway
Elisabeth Berge Nilsen
Department of Obstetrics and Gynecology, Stavanger University Hospital, 4068 Stavanger, Norway
Grete Alræk Iversen
Department of Obstetrics and Gynecology, Haukeland University Hospital, 5021 Bergen, Norway
Ragnar Kvie Sande
Department of Obstetrics and Gynecology, Stavanger University Hospital, 4068 Stavanger, Norway
Line Bjørge
Centre for Cancer Biomarkers CCBIO, Department of Clinical Science, University of Bergen, 5020 Bergen, Norway
Liv Cecilie Vestrheim Thomsen
Centre for Cancer Biomarkers CCBIO, Department of Clinical Science, University of Bergen, 5020 Bergen, Norway
High-grade serous ovarian carcinoma (HGSOC) is the most common and deadliest ovarian cancer subtype. Despite advances in treatment, the overall prognosis remains poor. Regardless of efforts to develop biomarkers to predict surgical outcome and recurrence risk and resistance, reproducible indicators are scarce. Exploring the complex tumor heterogeneity, serum profiling of metabolites and lipoprotein subfractions that reflect both systemic and local biological processes were utilized. Furthermore, the overall impact on the patient from the tumor and the treatment was investigated. The aim was to characterize the systemic metabolic effects of primary treatment in patients with advanced HGSOC. In total 28 metabolites and 112 lipoproteins were analyzed by nuclear magnetic resonance (NMR) spectroscopy in longitudinal serum samples (n = 112) from patients with advanced HGSOC (n = 24) from the IMPACT trial with linear mixed effect models and repeated measures ANOVA simultaneous component analysis. The serum profiling revealed treatment-induced changes in both lipoprotein subfractions and circulating metabolites. The development of a more atherogenic lipid profile throughout the treatment, which was more evident in patients with short time to recurrence, indicates an enhanced systemic inflammation and increased risk of cardiovascular disease after treatment. The findings suggest that treatment-induced changes in the metabolome reflect mechanisms behind the diversity in disease-related outcomes.
