Abstract
BackgroundSteroid hormones are essential signalling molecules in prostate cancer (PC). However, many studies focusing on liquid biomarkers fail to take the hormonal status of these patients into account. Steroid measurements are sensitive to bias caused by matrix effects, thus assessing potential matrix effects is an important step in combining circulating tumour DNA (ctDNA) analysis with hormone status. MethodsWe investigated the accuracy of multi-steroid hormone profiling in mechanically-separated plasma (MSP) samples and in plasma from CellSave Preservative (CS) tubes, that are typically used to obtain ctDNA, compared to measurements in serum. We performed multiplex steroid profiling by liquid chromatography–tandem mass spectrometry (LC–MS/MS) in samples obtained from ten healthy controls and ten castration-resistant prostate cancer (CRPC) patients. ResultsSteroid measurements were comparable between MSP and serum. A small but consistent decrease of 8–21% compared to serum was observed when using CS plasma, which was considered to be within the acceptable margin. The minimal residual testosterone levels of CRPC patients could be sensitively quantified in both MSP and CS samples. ConclusionsWe validated the use of MSP and CS samples for multi-steroid profiling by LC–MS/MS. The optimised use of these samples in clinical trials will allow us to gain further insight into the steroid metabolism in PC patients.
Highlights
Prostate cancer (PC) is a steroid-hormone dependent disease where androgens play a pivotal role in the evolution of the disease
Circulating steroid levels of 8 steroids were determined by LC–mass spectrometry (MS)/MS in plasma collected with CellSave Preservative (CS) and mechanically-separated plasma (MSP) tubes, respectively, and serum, all collected from 10 healthy control (HC) and 10 metastatic CRPC (mCRPC) patients
Low signal-to-noise ratios limited the reliability of DHT quantification, which could not be accurately quantified in two healthy control subjects as well as the mCRPC subjects
Summary
Prostate cancer (PC) is a steroid-hormone dependent disease where androgens play a pivotal role in the evolution of the disease. The continued importance of the androgen signalling pathway in castration-resistant prostate cancer (CRPC) is underlined by the survival benefits observed with second-line therapies such as the anti-androgen enzalutamide and adrenal ste roidogenesis inhibitor abiraterone [7,8,9,10]. Steroid measure ments are sensitive to bias caused by matrix effects, assessing potential matrix effects is an important step in combining circulating tumour DNA (ctDNA) analysis with hormone status. Methods: We investigated the accuracy of multi-steroid hormone profiling in mechanically-separated plasma (MSP) samples and in plasma from CellSave Preservative (CS) tubes, that are typically used to obtain ctDNA, compared to measurements in serum. We performed multiplex steroid profiling by liquid chromatogra phy–tandem mass spectrometry (LC–MS/MS) in samples obtained from ten healthy controls and ten castrationresistant prostate cancer (CRPC) patients. The optimised use of these samples in clinical trials will allow us to gain further insight into the steroid metabolism in PC patients
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