A Caenorhabditis elegans behavioral assay distinguishes early stage prostate cancer patient urine from controls

Abstract

Current 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 were compared to controls with 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.

Pond Assay for the Sensory Systems of Caenorhabditis elegans: A Novel Anesthesia-Free Method Enabling Detection of Responses to Extremely Low Chemical Concentrations

“…By using the PASS method, the olfactory system of C. elegans that might accurately sense odors at far lower concentrations than previously known will be investigated in the near future. Furthermore, this method can be applied to any technology and it can be utilized in various industrial fields, such as medicine and medical care [ 33 , 34 , 35 , 36 ], life sciences, veterinary medicine, agriculture and forestry, food, quantum science, and environmental fields.…”

Non-Invasive Cancer Detection in Canine Urine through C. elegans Chemotaxis

“…Further diagnosis and monitoring of symptoms is necessary to confirm the presence of cancer and its type. In addition, it has previously been shown that attractive VOCs are present in the urine during both early and late stages of cancer (20,22), so it is likely that in future assays, we can demonstrate the ability to screen for cancer at the earliest stages.…”

“…Study to accurately identify urine samples from canine cancer patients (Figure 1). Previous chemotaxis assays have used anywhere from three to six replicates to determine the mean CI (20)(21)(22). For canine urine assays, we often found variance in the response and magnitude in individual replicates within an assay (Supplementary Table 1).…”

“…These odorant signatures are detectable in samples acquired from animals such as dogs (18) and mice (19), and thus could serve as a marker for identifying cancer. It has been shown that C. elegans can quantitatively detect the presence of signature VOCs in both in culture media of cancer cells in vitro and in urine samples of human cancer patients through chemotaxis assays and through calcium imaging of the AWC neuron (20)(21)(22)(23). However, C. elegans has not yet been shown to identify cancerous VOC signatures in canine urine samples.…”

Scent test using Caenorhabditis elegans to screen for early-stage pancreatic cancer

“…Moreover, given that the Ras-MAPK pathway regulates meiosis and spout formation in C. elegans , such a pathway has been shown to reduce chemotaxis to odorants, and the exposure of the odorant isoamyl alcohol to C. elegans resulted in the activation of the MAP kinase in olfactory neurons within 10 s, suggesting that the Ras-MAPK pathway may be a candidate pathway involved in scent detection using C. elegans , although the underlying mechanisms for chemotaxis remain to be elucidated [ 13 , 14 , 32 , 33 ]. Eventually, recent study proposed that 2-octonone and pentanal levels were increased in urine of prostate cancer patients, compared to healthy controls, suggesting that both 2-octonone and pentanal higher levels in urine may be biomarkers of prostate cancer [ 34 ]. Moreover, very recent study of pancreatic ductal adenocarcinoma indicated that possible VOCs and metabolite biomarkers in urine were acetone, 2-pantanone, 4-methyl-2-heptanone, D-limonene, and levomenthol, though both chronic pancreatitis and PDAC shared common VOCs, so in the previous study, the authors could not fully discriminate both chronic pancreatitis and PDAC using GC-TOF-MS [ 35 ].…”