Accumulated metabolites of hydroxybutyric acid serve as diagnostic and prognostic biomarkers of ovarian high-grade serous carcinomas

Mika Hilvo, Ines De Santiago, Peddinti Gopalacharyulu, Wolfgand D. Schmitt, Jan Budczies, Marc Kuhberg, Manfred Dietel, Tero Aittokallio, Florian Markowetz, Carsten Denkert, Jalid Sehouli, Christian Frezza, Silvia Darb-Esfahani, Elena Ioana Braicu

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Abstract

Ovarian cancer is a heterogeneous disease of low prevalence, but poor survival. Early diagnosis is critical for survival, but it is often challenging because the symptoms of ovarian cancer are subtle and become apparent only during advanced stages of the disease. Therefore, the identification of robust biomarkers of early disease is a clinical priority. Metabolomic profiling is an emerging diagnostic tool enabling the detection of biomarkers reflecting alterations in tumor metabolism, a hallmark of cancer. In this study, we performed metabolomic profiling of serum and tumor tissue from 158 patients with high-grade serous ovarian cancer (HGSOC) and 100 control patients with benign or non-neoplastic lesions. We report metabolites of hydroxybutyric acid (HBA) as novel diagnostic and prognostic biomarkers associated with tumor burden and patient survival. The accumulation of HBA metabolites caused by HGSOC was also associated with reduced expression of succinic semialdehyde dehydrogenase (encoded by ALDH5A1), and with the presence of an epithelial-to-mesenchymal transition gene signature, implying a role for these metabolic alterations in cancer cell migration and invasion. In conclusion, our findings represent the first comprehensive metabolomics analysis in HGSOC and propose a new set of metabolites as biomarkers of disease with diagnostic and prognostic capabilities.
Original languageEnglish
Pages (from-to)796-804
JournalCancer Research
Volume76
Issue number4
DOIs
Publication statusPublished - 2016
MoE publication typeA1 Journal article-refereed

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Hilvo, M., De Santiago, I., Gopalacharyulu, P., Schmitt, W. D., Budczies, J., Kuhberg, M., Dietel, M., Aittokallio, T., Markowetz, F., Denkert, C., Sehouli, J., Frezza, C., Darb-Esfahani, S., & Braicu, E. I. (2016). Accumulated metabolites of hydroxybutyric acid serve as diagnostic and prognostic biomarkers of ovarian high-grade serous carcinomas. Cancer Research, 76(4), 796-804. https://doi.org/10.1158/0008-5472.CAN-15-2298