TY - JOUR
T1 - PCPro
T2 - a clinically accessible, circulating lipid biomarker signature for poor-prognosis metastatic prostate cancer
AU - Scheinberg, Tahlia
AU - Lin, Hui-Ming
AU - Fitzpatrick, Michael
AU - Azad, Arun A.
AU - Bonnitcha, Paul
AU - Davies, Amy
AU - Heller, Gillian
AU - Huynh, Kevin
AU - Mak, Blossom
AU - Mahon, Kate
AU - Sullivan, David
AU - Meikle, Peter J.
AU - Horvath, Lisa G.
N1 - Funding Information:
We gratefully acknowledge Lisa Graham (Chris O’Brien Lifehouse) and research nurses for the collection of blood specimens and clinical data, and Tony Maxwell for being our consumer representative. We also acknowledge the study participants. National Health and Medical Research Council of Australia (GNT1196225 to LGH, GNT1098647 to AAA, GNT1197190 to KH, GNT2009965 to PJM); Cancer Institute New South Wales (10/TPG/1‐04, 2018/TPG001); Australian Prostate Cancer Research Centre‐New South Wales; Australian Department of Health and Aging; the Movember Foundation and the Prostate Cancer Foundation of Australia (Revolutionary Team Award MRTA3); Cancer Council New South Wales (PG 10‐01); The Victorian Government’s Operational Infrastructure Support Program; Australian Government Research Training Program (RTP) Scholarship and University of Sydney Merit Award to BM; Australian Government Research Training Program (RTP) Scholarship and Sydney Catalyst Research Top-up Award to TS; Victorian Cancer Agency Clinical Research Fellowship (CRF14009) and Astellas Investigator‐Initiated Grant to AAA; ANZUP Noel Castan Fellowship to HML; Twin Towns Services Community Foundation to LGH. The funders had no roles in the design of the study; in the collection, analyses or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.
Publisher Copyright:
© 2023, The Author(s).
PY - 2023/5/5
Y1 - 2023/5/5
N2 - Background: 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. Methods: 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. Results: 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). Conclusions: 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.
AB - Background: 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. Methods: 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. Results: 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). Conclusions: 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.
UR - http://www.scopus.com/inward/record.url?scp=85158115739&partnerID=8YFLogxK
U2 - 10.1038/s41391-023-00666-2
DO - 10.1038/s41391-023-00666-2
M3 - Article
C2 - 37147359
AN - SCOPUS:85158115739
SN - 1365-7852
VL - 27
SP - 136
EP - 143
JO - Prostate Cancer and Prostatic Diseases
JF - Prostate Cancer and Prostatic Diseases
IS - 1
ER -
