Metabolomics and Prostate Cancer

We performed untargeted serum metabolomic profiling of two large population-based prostate cancer populations. Molecular features have been derived and explored for association with prostate cancer status (6,138 features, 475 subjects) and prostate cancer survival (5,209 features, 534 subjects). Assessment of metabolite features revealed two features as studywide significantly associated with prostate cancer status; however, due to low observed abundance we were not able to identify the molecular identity of these features. Among features indicated in pairwise analysis molecular identification revealed Caprolactam, L-Phosphatidic acid, and Peptide (Tyr-Lys-Thr) as possibly associated with prostate cancer aetiology. Genomewide assessment of the four top associated metabolite features implicated four genes PDE7B, NRG3, ILI3RA1 and UGT3A1 of which the association between metabolite feature 174.1_53 and gene ILI3RA1 was genome-wide significant (P = 1.4 x 10-8). This finding is interesting since although IL13RA1 itself has not been associated with prostate cancer, the alpha 2 chain of the same receptor (IL13RA2) has been reported to be differentially expressed in a metastatic prostate cancer cell line, and suggested as a target for prostate cancer treatment. In summary, several metabolite features associated with prostate cancer were discovered that warrant further investigation to advance our understanding of the underlying biological processes.
The original document contains color images.