SFEBES2022 Oral Communications Endocrine Cancer and Late Effects (6 abstracts)
Plasma metabolites correlate with disease in sdhx deficient cancer syndromes
Yasemin Cole 1 , Ifat Abramovich 2 , Jonatan Fernandes-Garcia 2 , France Docquier 1 , James MacFarlane 3 , Ben Challis 3 , Eamonn Maher 1 , Eyal Gottlieb 2 & Ruth Casey 1,3
1Department of Medical Genetics, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom; 2Technion Integrated Cancer Center, Israel Institute of Technology, Haifa, Israel; 3Department of Endocrinology, Cambridge University Hospital, Cambridge Biomedical Research Centre, Addenbrooke’s Hospital, Cambridge, United Kingdom
Approximately 40% of phaeochromocytomas and paragangliomas (PPGL) are associated with a germline mutation. These individuals have a lifetime tumour risk and in the case of SDHx germline mutations, there is a risk of multiple tumours and malignancy. We sought to discover plasma metabolites associated with succinate dehydrogenase (SDH) deficiency and tumorigenesis for potential use as predictive and/or prognostic biomarkers. Plasma samples were collected prospectively from a clinically well-characterized patient cohort (Cambridge, UK) with SDHx and non-SDHx variants. We performed liquid chromatography/mass spectroscopy (LC/MS) analysis of polar compounds profiling 124 enrolled patients. Concurrently, we collected clinical data including; plasma metanephrine and 3-methoxytyramine measurements and imaging characteristics. Of the 124 patients (age range 17 – 81, mean 45), 45.9% had an SDHx germline predisposition, of which 47.4% (27/57) had a current benign/metastatic tumour and 21.1% (12/57) had a previous tumour. We found that the levels of the proposed metabolic biomarker, succinate, were not significantly altered in SDHx carriers and patients with SDH deficient tumours. The untargeted analysis of the plasma (n=72) detected 2300 chromatographic features and we ranked them based on their discriminatory ability. We discovered one with mass-to-charge (m/z) = 328.24 was significantly elevated in SDHx carriers compared to non-SDHx carriers with AUROC=0.765, Mann-Whitney U test P-value=0.0074, and Hedge’s g=-1.01. Furthermore, compared to SDHx carriers with no current tumour or past tumour, we found significantly altered chromatographic signals (m/z=304.29, AUROC=0.75, P-value=0.011, Hedge’s g=-0.228; m/z=512.33, AUROC=0.726, P-value=0.022, Hedge’s g=0.929; m/z=585.27, AUROC=0.75, P-value=0.011, Hedge’s g=-0.8) in SDHx patients with benign and metastatic tumours. Identification of these features is in progress. These preliminary findings are being extended in further patients/samples and SDHx knockout mouse models but suggest several LC/MS signals may be pursued as candidate diagnostic biomarkers to track tumour development, progression and recurrence.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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