Abstract 922: Body composition and metabolic dysfunction really matter for the achievement of better outcomes in high-grade serous ovarian cancer

作者：Mauricio Cuello-Fredes, Fernán Gómez‐Valenzuela, Ignacio Wichmann, Felipe Suárez, Sumie Kato, Jorge Brañes, Elisa Orlandini, Carolina Ibáñez · 发表于：Cancer Research · 年份：2023 · DOI：10.1158/1538-7445.am2023-922 · 研究领域：Cancer, Lipids, and Metabolism、Cancer-related molecular mechanisms research、Folate and B Vitamins Research

Abstract Our objective was to evaluate the impact of body composition (BC), beyond body mass index (BMI), and lipid metabolism disorders on therapeutic responses and outcomes in high-grade serous ovarian cancer (HGSOC).Methods: 123 and 415 patients with advanced HGSOC from two cohorts (PUC and TCGA) were analyzed. Databases containing clinical/genomic variables were built-up. BC was estimated using the measurement of adiposity (e.g., Whole body Adipose Tissue [WBAT]) and muscle mass (Lumbar muscle area to vertebral body at L4-level, [PLVI]) by CT-scan. A list of 425 genes linked to obesity and lipid metabolism was used to identify clusters using non-negative matrix factorization. GSEA, Gene Ontology, KEGG pathways enrichment, and Ecotyper analyzes were also made. Survival curves and Cox-regression models were also built-up. Results: We identified four BC types and two clusters that, unlike BMI, effectively correlate with survival regardless of achieving optimal debulking or complete response. Mention deserves central sarcopenia, which was associated with worse survival in any condition. So also, that recovering a normal BC and adding medications to correct metabolism disorders (e.g., statins) could have a positive impact on outcomes. Along with this, we showed that micro-environments depleted of immune cells predominate in HGSOC, something more evident in the BC type (High WBAT/Low PLVI) and cluster (Obesity/Lipid Metabolism Type I) with worse prognosis. Conclusions: Here, we...