SFEBES2025 Oral Communications Endocrine Cancer and Late Effects (6 abstracts)
Serum untargeted metabolomics reveals widespread metabolic dysregulation in adrenocortical carcinoma
Vasileios Chortis 1,2 , Irina Bancos 3 , Alessandro Prete 1,2,4 , Angela E. Taylor 1,2 , Dimitra A. Vassiliadi 5 , Darko Kastelan 6 , Antoine Tabarin 7 , Marcus Quinkler 8 , Letizia Canu 9 , Graeme Eisenhofer 10 , M. Conall Dennedy 11 , Grethe A. Ueland 12 , Felix Beuschlein 13,14 , Martin Fassnacht 15 , Urszula Ambroziak 16 , Warwick B. Dunn 17 & Wiebke Arlt 1,18,19
1Department of Metabolism and Systems Science, University of Birmingham, Birmingham, United Kingdom; 2Centre for Endocrinology, Diabetes and Metabolism, Birmingham Health Partners, Birmingham, United Kingdom; 3Division of Endocrinology, Metabolism and Nutrition, Mayo Clinic, Rochester, USA; 4NIHR Birmingham Biomedical Research Centre, University of Birmingham and University Hospitals Birmingham NHS Foundation Trust, Birmingham, United Kingdom; 5Department of Endocrinology, Diabetes and Metabolism, Evangelismos Hospital, Athens, Greece; 6Department of Endocrinology, University Hospital Centre Zagreb, Zagreb, Croatia; 7Department of Endocrinology, Hôpital Haut Lévêque, CHU de Bordeaux, Pessac, France; 8Endocrinology in Charlottenburg, Berlin, Germany; 9Department of Experimental and Clinical Biomedical Sciences, University of Florence, Florence, Italy; 10Institute of Clinical Chemistry and Laboratory Medicine, University Hospital Carl Gustav Carus, Technical University, Dresden, Germany; 11School of Medicine, National University of Ireland Galway, Galway, Ireland; 12Department of Clinical Science, University of Bergen, Bergen, Norway; 13Medizinische Klinik and Poliklinik IV, Klinikum der Universität, Ludwig-Maximilians- Universitaüt Muünchen, Munich, Germany; 14Department of Endocrinology, Diabetology and Clinical Nutrition, University Hospital Zurich, Zurich, Switzerland; 15Comprehensive Cancer Center Mainfranken and Central Laboratory, University Hospital Wuürzburg, University of Wuürzburg, Wuürzburg, Germany; 16Department of Internal Medicine and Endocrinology, Medical University of Warsaw, Warsaw, Poland; 17Department of Biochemistry, Cells and Systems Biology, Centre for Metabolomics Research, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, United Kingdom; 18MRC Laboratory of Medical Sciences, London, United Kingdom; 19Institute of Clinical Sciences, Faculty of Medicine, Imperial College London, London, United Kingdom
Dysregulation of cell metabolism is a hallmark feature of cancer, which remains under-explored in adrenocortical carcinoma (ACC). Dissecting ACC tumour metabolism is of high translational importance, with the potential to identify new treatment targets as well as diagnostic or prognostic biomarkers. In this prospective, multi-centre study, we collected pre-operative serum samples from 54 patients with ACC (65% women; 11% with isolated glucocorticoid excess; 7% with isolated androgen excess; 52% with mixed hormone excess; 22% metastatic at the time of tumour diagnosis) and 291 age-, sex- and body mass index-matched controls with benign, non-aldosterone-producing adrenocortical adenomas (ACA; 36% non-functioning, 48% mild autonomous cortisol secretion, and 16% adrenal Cushing’s syndrome). We completed untargeted profiling of polar and non-polar metabolites by ultra-high performance liquid chromatography-tandem mass spectrometry. ACC patients had a distinct serum metabolome, with 437 significantly dysregulated metabolites compared to ACA (false discovery rate [FDR] <0.05), of which 24 showed a >2-fold change between the two groups. Pathway analysis revealed widespread dysregulation of amino-acid and nucleotide metabolism, including arginine and proline metabolism; branched-chain amino-acid biosynthesis; glycine and serine metabolism; alanine, aspartate and glutamate metabolism; and pyrimidine metabolism (FDR<0.05). There was also wide dysregulation of steroid metabolites and lipids, most prominently affecting glycerophospholipids, ceramides and sphingolipids, and triglycerides. The extensive changes in the serum metabolome of ACC patients in comparison to patients with ACA persisted when patients were stratified for the presence of Cushing’s syndrome. There were also notable differences among ACC patients depending on whether the tumour had a low (<10%), intermediate (10-19%) or high (≥20%) Ki67 proliferation index (n=5 dysregulated metabolites, FDR<0.05). This study reveals for the first time distinct and extensive changes in the serum metabolome of ACC patients, providing new insights into tumour biology.
Volume 109
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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