Session: Advances in Mass Spectrometry:

Urinary volatile organic compound (VOC) biomarkers for cancer are byproducts of dysregulated metabolic pathways. While VOC biomarker results from humans and mice can be qualitatively examined by comparing and contrasting molecules published from independent studies, a question which has yet to be answered is whether VOC results obtained from murine models can directly and quantitatively translate to human outcomes. Urine was analyzed from mice before and after they were injected with prostate cancer tumor cells (from nine mice with urine collected post injection and nine prior to injection) and from men diagnosed with aggressive prostate cancer and controls (15 men with ISUP > 2, and 38 men with ISUP = 0). All urine samples were analyzed by headspace-solid phase microextraction (HS-SPME) coupled with gas chromatography-mass spectrometry quadrupole time-of-flight (GC-MS-QTOF). Controls were run each day to determine instrument and method fidelity. Chromatograms were deconvoluted and spectrally aligned to identify conserved VOCs between samples and data sets. There was an overlap of 53 VOCs that were found in both murine and human data sets, with 6 of these VOCs qualified as potential biomarkers. A panel of four VOCs could distinguish prostate cancer in mice and humans with the area under the curve (AUC) of the receiver operator characteristic (ROC) of 0.89 in the mouse (training set) and 0.82 in the human (testing set), giving the model 83% accuracy in the mouse set and 75% accuracy in the human set. This panel was comprised of volatile medium-chain ketones and terpenes, correlating with previous VOC biomarker analyses for prostate cancer. This study shows that similar processes of prostate cancer-induced metabolic dysregulation (as shown by identical and similar VOC biomarkers) occur in both mice and men.

Hiroki Yokota

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