Abstract
ABSTRACTCurrent methods for non-invasive prostate cancer (PrCa) detection have a high false-positive rate and often result in unnecessary biopsies. Previous work has suggested that urinary volatile organic compound (VOC) biomarkers may be able to distinguish PrCa cases from benign disease. The behavior of the nematode Caenorhabditis elegans has been proposed as a tool to take advantage of these potential VOC profiles. To test the ability of C. elegans Bristol N2 to distinguish PrCa cases from controls, we performed chemotaxis assays using human urine samples collected from men screened for PrCa. Behavioral response of nematodes towards diluted urine from PrCa cases was compared to response to samples from cancer-free controls. Overall, we observed a significant attraction of young adult-stage C. elegans nematodes to 1:100 diluted urine from confirmed PrCa cases and repulsion of C. elegans to urine from controls. When C. elegans chemotaxis index was considered alongside prostate-specific antigen levels for distinguishing cancer from cancer-free controls, the accuracy of patient classification was 81%. We also observed behavioral attraction of C. elegans to two previously reported VOCs to be increased in PrCa patient urine. We conclude nematode behavior distinguishes PrCa case urine from controls in a dilution-dependent manner.
Highlights
Many cancers have altered metabolic pathways that support, or may even cause, malignancy (Ward and Thompson, 2012)
C. elegans N2 are attracted to previously identified volatile organic compound (VOC) candidates for prostate cancer (PrCa) classification To determine if C. elegans N2 displayed a behavioral response to candidate VOCs, chemotaxis assays were performed using diluted 2-octonone or pentanal as test samples
Accumulating evidence suggests that the metabolomic profiles of patients with prostate cancer can be distinguished from normal patients and this difference could potentially be measured through blood or urine samples (Kdadra et al, 2019)
Summary
Many cancers have altered metabolic pathways that support, or may even cause, malignancy (Ward and Thompson, 2012) Detection of these cancer-related metabolites or volatile compounds in blood and urine would provide an ideal means of non-invasive early cancer detection. Even in the early stages of malignancy, there is evidence that cancer patients emit odors that can be accurately detected by canine and murine olfaction Animal systems that have a naturally occurring odor discrimination for cancer patient samples could be a powerful tool for developing early cancer detection technology
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