Metabolomic evaluation of the response to endocrine therapy in patients with prostate cancer

Abstract

Timely evaluation of the response to endocrine therapy in patients with prostate cancer (PCa) may optimize treatment regimens and improve long-term prognosis. We used the liquid chromatography-mass spectrometry (LC-MS)-based metabolomic technique to identify serum biomarkers indicative of disease progression and therapeutic benefit. The mean serum levels of seven metabolites, including deoxycholic acid (DCA), glycochenodeoxycholate (GCDC), l-tryptophan, docosapentaenoic acid (DPA), arachidonic acid, deoxycytidine triphosphate, and pyridinoline, differed significantly between untreated PCa patients and healthy controls. In patients who did not develop castration-resistant prostate cancer (CRPC) for at least 2 years (good responders), these metabolite levels reverted to near healthy control levels during endocrine therapy. In contrast, the metabolite levels remained abnormal in patients who developed CRPC within 1 year (poorly responsive patients). Three of these biomarkers (DCA, GCDC, and DPA) are mainly involved in cholesterol metabolism, underscoring the importance of elevated cholesterol to PCa progression. These metabolites may serve as predictive biomarkers for assessing the therapeutic response of PCa patients to endocrine therapy.

Keywords: DCA; DPA; Endocrine therapy; GCDC; Metabolomics; Prostate cancer.