Pre-diagnostic Serum Metabolomic Profiling of Prostate Cancer Survival

Pre-diagnostic Serum Metabolomic Profiling of Prostate Cancer Survival Abstract Impaired metabolism may play a role in the development and lethality of prostate cancer, yet a comprehensive analysis of the interrelationships appears lacking. We measured 625 metabolites using ultrahigh performance LC/MS-GC/MS of prediagnostic serum from 197 prostate cancer cases in the ATBC Study (ages at diagnosis, 55-86 years). Cox proportional hazards models estimated associations between circulating metabolites and prostate cancer mortality for 1-standard deviation (SD) differences (log-metabolite scale), adjusted for age, year of diagnosis, and disease stage. Associations between metabolite chemical classes and survival were examined through pathway analysis, and Cox models assessed the relationship with a sterol/steroid metabolite principal component analysis factor score. Elevated serum N-oleoyl taurine was significantly associated with prostate cancer-specific mortality (HR=1.72 per 1-SD, p<0.00008, Bonferroni corrected threshold=0.05/625; HR=3.6 for highest vs lowest tertile, p<0.001). Pathway analyses revealed a statistically significant association between lipids and prostate cancer death (p<0.006, Bonferroni-corrected threshold=0.05/8), and sterol/steroid metabolites showed the strongest chemical sub-class association (p=0.0014, Bonferroni-corrected threshold=0.05/45). In the principal component analysis, a 1-SD increment in the sterol/steroid metabolite score increased the risk of prostate cancer death by 46%. Prediagnostic serum N-oleoyl taurine and sterol/steroid metabolites were associated with prostate cancer survival. metabolomic profile, prostate cancer mortality, N-oleoyl taurine, sex sterol/steroid Published by Oxford University Press on behalf of The Gerontological Society of America 2018. This work is written by (a) US Government employee(s) and is in the public domain in the US. This work is written by (a) US Government employee(s) and is in the public domain in the US. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png The Journals of Gerontology Series A: Biomedical Sciences and Medical Sciences Oxford University Press

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Publisher
Oxford University Press
Copyright
Published by Oxford University Press on behalf of The Gerontological Society of America 2018. This work is written by (a) US Government employee(s) and is in the public domain in the US.
ISSN
1079-5006
eISSN
1758-535X
D.O.I.
10.1093/gerona/gly128
Publisher site
See Article on Publisher Site

Abstract

Abstract Impaired metabolism may play a role in the development and lethality of prostate cancer, yet a comprehensive analysis of the interrelationships appears lacking. We measured 625 metabolites using ultrahigh performance LC/MS-GC/MS of prediagnostic serum from 197 prostate cancer cases in the ATBC Study (ages at diagnosis, 55-86 years). Cox proportional hazards models estimated associations between circulating metabolites and prostate cancer mortality for 1-standard deviation (SD) differences (log-metabolite scale), adjusted for age, year of diagnosis, and disease stage. Associations between metabolite chemical classes and survival were examined through pathway analysis, and Cox models assessed the relationship with a sterol/steroid metabolite principal component analysis factor score. Elevated serum N-oleoyl taurine was significantly associated with prostate cancer-specific mortality (HR=1.72 per 1-SD, p<0.00008, Bonferroni corrected threshold=0.05/625; HR=3.6 for highest vs lowest tertile, p<0.001). Pathway analyses revealed a statistically significant association between lipids and prostate cancer death (p<0.006, Bonferroni-corrected threshold=0.05/8), and sterol/steroid metabolites showed the strongest chemical sub-class association (p=0.0014, Bonferroni-corrected threshold=0.05/45). In the principal component analysis, a 1-SD increment in the sterol/steroid metabolite score increased the risk of prostate cancer death by 46%. Prediagnostic serum N-oleoyl taurine and sterol/steroid metabolites were associated with prostate cancer survival. metabolomic profile, prostate cancer mortality, N-oleoyl taurine, sex sterol/steroid Published by Oxford University Press on behalf of The Gerontological Society of America 2018. This work is written by (a) US Government employee(s) and is in the public domain in the US. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Journal

The Journals of Gerontology Series A: Biomedical Sciences and Medical SciencesOxford University Press

Published: Jun 7, 2018

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