Efficiency of Gastrointestinal Cancer Detection by Nematode-NOSE (N-NOSE)

Kusumoto, Hirotake; Tashiro, Kotaro; Shimaoka, Syunji; Tsukasa, Koichiro; Baba, Yukiko; Furukawa, Saori; Furukawa, Junichiro; Niihara, Toru; Hirotsu, Takaaki; Uozumi, Takayuki

doi:10.21873/invivo.11747

Cited by 21 publications

(24 citation statements)

References 22 publications

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“…The first approach is to develop high-throughput and reproducible technology that can use the animal behavior preference itself as a diagnostic assay (e.g. the ‘N-nose’ demonstrated by Hirotsu et al, 2015 and Kusumoto et al, 2020) . Another possibility is to use the behavioral assay as an unbiased sensor system that could be coupled with a discovery method such as GC-MS.…”

Section: Discussionmentioning

confidence: 99%

“… Hirotsu et al (2015) further showed that the C. elegans behavioral response worked strictly through G-protein coupled receptor (GPCR) mediated signaling and via chemosensory neurons known to be important for sensing VOCs. More recently and using a similar chemotaxis assay, a report by Kusumoto et al (2020) demonstrated that C. elegans accurately differentiates between matched preoperative and postoperative samples from patients that underwent gastrointestinal cancer resection. Thus, the natural behavioral response of C. elegans to cancer patient urine may provide a useful tool for detecting cancer VOCs at early, treatable stages or for monitoring residual disease.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2021

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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.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

et al. 2021

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“…The N-NOSE showed different behaviors before and after tumor removal via surgical operation, suggesting its usefulness as a highly sensitive method to monitor patients postoperatively [34]. The results were confirmed through the analysis of a relatively large study of 180 urine samples from patients with gastrointestinal cancer and 76 samples from healthy participants, indicating the method's high sensitivity as a gastrointestinal cancer screening test, with a significant value of 0.80 in the receiver operating characteristic analysis, even in early stage cancers [35].…”

Section: Caenorhabditis Elegans (C Elegans)mentioning

confidence: 66%

State-of-the-Art Technology of Model Organisms for Current Human Medicine

et al. 2020

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Since the 1980s, molecular biology has been used to investigate medical field mechanisms that still require the use of crude biological materials in order to achieve their necessary goals. Transcription factor-induced pluripotent stem cells are used in regenerative medicine to screen drugs and to support lost tissues. However, these cells insufficiently reconstruct whole organs and require various intact cells, such as damaged livers and diabetic pancreases. For efficient gene transfer in medical use, virally mediated gene transfers are used, although immunogenic issues are investigated. To obtain efficient detective and diagnostic power in intractable diseases, biological tools such as roundworms and zebrafish have been found to be useful for high-throughput screening (HST) and diagnosis. Taken together, this biological approach will help to fill the gaps between medical needs and novel innovations in the field of medicine.

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“…To utilize this system as a screening test for patients with early-stage PDAC, higher specificity is imperative. Despite the high specificity in previous studies [ 15 , 17 ], an excessive number of participants would need to be sent for detailed examination for PDAC. Moreover, the suitable urine dilution for early PDAC remains under investigation.…”

Section: Discussionmentioning

confidence: 99%

“…This biological diagnosis had a reported sensitivity of 95.8%, which was also acceptable even in patients in early-stage of cancer. Furthermore, reports have shown that this test demonstrated high sensitivity in cases of gastrointestinal cancers and negative changes in the postoperative period [ 16 , 17 ]. Moreover, this test could discriminate urine in a mouse model of pancreatic cancer [ 18 ].…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2021

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Although early detection and diagnosis are indispensable for improving the prognosis of patients with pancreatic cancer, both have yet to be achieved. Except for pancreatic cancer, other cancers have already been screened through scent tests using animals or microorganisms, including Caenorhabditis elegans . While such a method may greatly improve the prognosis of pancreatic cancer, no studies have investigated the same, mainly given the difficulty of collecting suitable samples from patients with early-stage pancreatic cancer. In this study, we organized a nationwide study group comprising high-volume centers throughout Japan to collect patients with very-early-stage pancreatic cancer (stage 0 or IA). We initially performed an open-label study involving 83 cases (stage 0–IV), with subsequent results showing significant differences after surgical removal in stage 0–IA (×10 dilution: p < 0.001; ×100 dilution: p < 0.001). Thereafter, a blinded study on 28 cases (11 patients with stage 0 or IA disease and 17 healthy volunteers) was conducted by comparing very-early-stage pancreatic cancer patients with healthy volunteers to determine whether C. elegans could detect the scent of cancer for the diagnosis of early-stage pancreatic cancer. Preoperative urine samples had a significantly higher chemotaxis index compared to postoperative samples in patients with pancreatic cancer [×10 dilution: p < 0.001, area under the receiver operating characteristic curve (AUC) = 0.845; ×100 dilution: p < 0.001, AUC = 0.820] and healthy volunteers (×10 dilution: p = 0.034; ×100 dilution: p = 0.088). Moreover, using the changes in preoperative and postoperative chemotaxis index, this method had a higher sensitivity for detecting early pancreatic cancer compared to existing diagnostic markers. The clinical application C. elegans for the early diagnosis of cancer can certainly be expected in the near future.

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Efficiency of Gastrointestinal Cancer Detection by Nematode-NOSE (N-NOSE)

Cited by 21 publications

References 22 publications

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

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

State-of-the-Art Technology of Model Organisms for Current Human Medicine

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

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