Repository logo
 

Accumulated Metabolites of Hydroxybutyric Acid Serve as Diagnostic and Prognostic Biomarkers of Ovarian High-Grade Serous Carcinomas.

Accepted version
Peer-reviewed

No Thumbnail Available

Type

Article

Change log

Authors

Hilvo, Mika 
de Santiago, Ines 
Gopalacharyulu, Peddinti 
Schmitt, Wolfgang D 
Budczies, Jan 

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.

Description

Keywords

Biomarkers, Tumor, Carcinoma, Ovarian Epithelial, Cystadenocarcinoma, Serous, Female, Humans, Hydroxybutyrates, Neoplasm Grading, Neoplasms, Glandular and Epithelial, Ovarian Neoplasms, Prognosis, Survival Analysis, Transcription Factors

Journal Title

Cancer Res

Conference Name

Journal ISSN

0008-5472
1538-7445

Volume Title

76

Publisher

American Association for Cancer Research (AACR)
Sponsorship
Medical Research Council (MC_UU_12022/6)
Cancer Research UK (C14303/A17197)
Cancer Research UK (CB4320)
MRC (unknown)
Cancer Research UK (A19274)