Format

Send to

Choose Destination
See comment in PubMed Commons below
J Proteome Res. 2014 Feb 7;13(2):1088-100. doi: 10.1021/pr401106h. Epub 2013 Dec 31.

Metabolomic profiling identifies biochemical pathways associated with castration-resistant prostate cancer.

Author information

1
Verna and Marrs McLean Department of Biochemistry and Molecular Biology, ‡Alkek Center for Molecular Discovery, §Molecular and Cellular Biology, and ∥Department of Surgery, Baylor College of Medicine , Houston, Texas 77030, United States.

Abstract

Despite recent developments in treatment strategies, castration-resistant prostate cancer (CRPC) is still the second leading cause of cancer-associated mortality among American men, the biological underpinnings of which are not well understood. To this end, we measured levels of 150 metabolites and examined the rate of utilization of 184 metabolites in metastatic androgen-dependent prostate cancer (AD) and CRPC cell lines using a combination of targeted mass spectrometry and metabolic phenotyping. Metabolic data were used to derive biochemical pathways that were enriched in CRPC, using Oncomine concept maps (OCM). The enriched pathways were then examined in-silico for their association with treatment failure (i.e., prostate specific antigen (PSA) recurrence or biochemical recurrence) using published clinically annotated gene expression data sets. Our results indicate that a total of 19 metabolites were altered in CRPC compared to AD cell lines. These altered metabolites mapped to a highly interconnected network of biochemical pathways that describe UDP glucuronosyltransferase (UGT) activity. We observed an association with time to treatment failure in an analysis employing genes restricted to this pathway in three independent gene expression data sets. In summary, our studies highlight the value of employing metabolomic strategies in cell lines to derive potentially clinically useful predictive tools.

PMID:
24359151
PMCID:
PMC3975657
DOI:
10.1021/pr401106h
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for American Chemical Society Icon for PubMed Central
    Loading ...
    Support Center