Using comprehensive plasma lipidomic profiling from men with metastatic castration-resistant prostate cancer (mCRPC), we have previously identified a poor-prognostic lipid profile associated with shorter overall survival (OS). In order to translate this biomarker into the clinic, these men must be identifiable via a clinically accessible, regulatory-compliant assay.
A single regulatory-compliant liquid chromatography-mass spectrometry assay of candidate lipids was developed and tested on a mCRPC Discovery cohort of 105 men. Various risk-score Cox regression prognostic models of OS were built using the Discovery cohort. The model with the highest concordance index (PCPro) was chosen for validation and tested on an independent Validation cohort of 183 men.
PCPro, the lipid biomarker, contains Cer(d18:1/18:0), Cer(d18:1/24:0), Cer(d18:1/24:1), triglycerides and total cholesterol. Within the Discovery and Validation cohorts, men who were PCPro positive had significantly shorter OS compared to those who were PCPro negative (Discovery: median OS 12.0 months vs 24.2 months, hazard ratio (HR) 3.75 [95% confidence interval (CI) 2.29-6.15], p < 0.001, Validation: median OS 13.0 months vs 25.7 months, HR = 2.13 [95% CI 1.46-3.12], p < 0.001).
We have developed PCPro, a lipid biomarker assay capable of prospectively identifying men with mCRPC with a poor prognosis. Prospective clinical trials are required to determine if men who are PCPro positive will benefit from therapeutic agents targeting lipid metabolism.
Prostate cancer and prostatic diseases. 2023 May 05 [Epub ahead of print]
Tahlia Scheinberg, Hui-Ming Lin, Michael Fitzpatrick, Arun A Azad, Paul Bonnitcha, Amy Davies, Gillian Heller, Kevin Huynh, Blossom Mak, Kate Mahon, David Sullivan, Peter J Meikle, Lisa G Horvath
Medical Oncology, Chris O'Brien Lifehouse, Camperdown, NSW, Australia., Advanced Prostate Cancer Group, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia., NSW Health Pathology, Department of Chemical Pathology, Royal Prince Alfred Hospital, Camperdown, NSW, 2050, Australia., Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia., University of Sydney, Camperdown, NSW, Australia., Department of Medical Oncology, Monash Health, Melbourne, VIC, Australia., Baker Heart and Diabetes Institute, Melbourne, VIC, Australia., Medical Oncology, Chris O'Brien Lifehouse, Camperdown, NSW, Australia. .