Integrative Systemic and Local Metabolomics with Impact on Survival in High-Grade Serous Ovarian Cancer
- Author(s)
- Anna Bachmayr-Heyda, Stefanie Aust, Katharina Auer, Samuel M. Meier, Klaus G. Schmetterer, Sabine Dekan, Christopher Gerner, Dietmar Pils
- Abstract
Purpose: Cancer metabolism is characterized by alterations including aerobic glycolysis, oxidative phosphorylation, and need of fuels and building blocks. Experimental Design: Targeted metabolomics of preoperative and follow-up sera, ascites, and tumor tissues, RNA sequencing of isolated tumor cells, local and systemic chemokine, and local immune cell infiltration data from up to 65 high-grade serous ovarian cancer patients and 62 healthy controls were correlated to overall survival and integrated in a Systems Medicine manner. Results: Forty-Three mainly (poly)unsaturated glycerophospholipids and four essential amino acids (citrulline) were significantly reduced in patients with short compared with long survival and healthy controls. The glycerophospholipid fingerprint is identical to the fingerprint from isolated (very) low-density lipoproteins (vLDL), indicating that the source of glycerophospholipids consumed by tumors is (v)LDL. A glycerophospholipid- score (HR, 0.46; P 0.007) and a 100-gene signature(HR, 0.65;P0.004)confirmed the independentimpact on survival in training (n65) and validation (n 165) cohorts. High concentrations of LDLs and glycerophospholipids were independently predictors for favorable survival. Patients with low glycerophospholipids presented with more systemic inflammation (C-reactive protein and fibrinogen negatively and albumin positively correlated) but less adaptive immune cell tumor infiltration (lower tumor and immune cell PD-L1 expression), less oxygenic respiration and increased triglyceride biosynthesis in tumor cells, and lower histone expressions, correlating with higher numbers of expressed genes and more transcriptional noise, a putative neo-pluripotent tumor cell phenotype. Conclusions: Low serum phospholipids and essential amino acids are correlated with worse outcome in ovarian cancer, accompanied by a specific tumor cell phenotype.
- Organisation(s)
- Department of Analytical Chemistry, Mass Spectrometry Centre
- External organisation(s)
- Medizinische Universität Wien, Cardiff University
- Journal
- Clinical Cancer Research
- Volume
- 23
- Pages
- 2081-2092
- No. of pages
- 12
- ISSN
- 1078-0432
- DOI
- https://doi.org/10.1158/1078-0432.CCR-16-1647
- Publication date
- 04-2017
- Peer reviewed
- Yes
- Austrian Fields of Science 2012
- 104002 Analytical chemistry, 302055 Oncology
- Keywords
- ASJC Scopus subject areas
- Oncology, Cancer Research
- Sustainable Development Goals
- SDG 3 - Good Health and Well-being
- Portal url
- https://ucrisportal.univie.ac.at/en/publications/4b0702ed-c68f-405c-bceb-e90c7593b5b6