Oncotarget

Research Papers:

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

Ayumu Asai, Masamitsu Konno, Miyuki Ozaki, Koichi Kawamoto, Ryota Chijimatsu, Nobuaki Kondo, Takaaki Hirotsu and Hideshi Ishii _

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Oncotarget. 2021; 12:1687-1696. https://doi.org/10.18632/oncotarget.28035

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Abstract

Ayumu Asai1,2, Masamitsu Konno1,4, Miyuki Ozaki1, Koichi Kawamoto1,5, Ryota Chijimatsu1, Nobuaki Kondo1,3, Takaaki Hirotsu1,3 and Hideshi Ishii1

1 Center of Medical Innovation and Translational Research (CoMIT), Graduate School of Medicine, Osaka University, Suita, Osaka, Japan

2 Artificial Intelligence Research Center, Institute of Scientific and Industrial Research, Osaka University, Ibaraki, Osaka, Japan

3 Hirotsu Bio Science Inc., Chiyoda-Ku, Tokyo 102-0094, Japan

4 Present address: Research Institute for Biomedical Sciences, Tokyo University of Science, Chiba, Japan

5 Present address: Kinnki Regional Bureau of Health and Welfare, Osaka, Japan

Correspondence to:

Hideshi Ishii, email: hishii@gesurg.med.osaka-u.ac.jp

Keywords: Caenorhabditis elegans; early-stage pancreatic cancer; scent test; biomarker; diagnosis

Received: May 07, 2021     Accepted: July 13, 2021     Published: August 17, 2021

Copyright: © 2021 Asai et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

ABSTRACT

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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