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. 2024 Dec 18;24(1):1544.
doi: 10.1186/s12885-024-13327-x.

Evaluation of N-NOSE as a surveillance tool for recurrence in gastric and esophageal cancers: a prospective cohort study

Sayuri Iitaka  1 , Akihiro Kuroda  1 , Tomonori Narita  1 , Hideyuki Hatakeyama  2 , Masayo Morishita  2 , Umbhorn Ungkulpasvich  2 , Takaaki Hirotsu  2 , Eric di Luccio  2 , Koichi Yagi  1 , Yasuyuki Seto  3   4
Affiliations

Evaluation of N-NOSE as a surveillance tool for recurrence in gastric and esophageal cancers: a prospective cohort study

Sayuri Iitaka et al. BMC Cancer. .

Erratum in

Abstract

Objective: Early detection of recurrent gastric and esophageal cancers remains a critical challenge. Innovative and non-invasive cancer screening technologies, such as N-NOSE, can improve early detection. N-NOSE is a urine-based scent test that leverages the olfactory abilities of the nematode C. elegans. For the first time, this prospective study evaluates the efficacy of the N-NOSE chemotaxis index as a novel biomarker for postoperative surveillance and recurrence in patients with upper gastrointestinal cancers.

Methods: A two-year prospective cohort study was conducted at The University of Tokyo Hospital, involving 40 patients with gastric and esophageal cancers. Urine samples were collected pre- and postoperatively and analysed using the N-NOSE technique.

Results: In cases of recurrence with vascular invasion, the chemotaxis index at 100-fold urine dilution was significantly elevated compared to the non-recurrence group.

Conclusion: This study suggests the potential of N-NOSE as an effective follow-up tool for patients with upper gastrointestinal cancer, particularly those with vascular invasion. While N-NOSE has been validated to distinguish between cancer and non-cancer, and its performance compared to traditional markers has been proven, it has not been studied for recurrence. Our data highlights, for the first time, the capability of N-NOSE in the surveillance of cancer recurrence.

Keywords: Caenorhabditis elegans (C. elegans); Gastric cancer; Nematode-nose (N-NOSE); Oesophageal cancer; Urine.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: All procedures followed in this study were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the World Medical Association Declaration of Helsinki. The institutional Ethical Review Board of the University of Tokyo Hospital approved this study (2020122NI). This study was registered with UMIN (UMIN000042740). Informed consent statement: We obtained written informed consent from all patients prior to all study-related procedures in this study. Consent for publication: Not applicable. Competing interests: T.H. is the CEO and founder of Hirotsu Bio Science Inc.; E.d.L., H.H., M.M., and U.U. are Hirotsu Bio Science Inc. employees.

Figures

Fig. 1
Fig. 1
Preoperative chemotherapy regimen. 10 patients in this study received chemotherapy in the method of the chemotherapy regimen that repeated 3 times the 21-day cycle of DCF medicine administration schedule. Docetaxel (70 mg/m2), Cisplatin (70 mg/m2) and 5-fluorouracil (5-FU, 700 mg/m2) were administered on the first day of the cycle and only 5-FU was continued every day to 5th day of the cycle. Then the rest 16 days (6th −21th day) had no medicine administration
Fig. 2
Fig. 2
Schematics of urine sampling. Urine samples were collected 6 times, before chemotherapy and/or surgery, at 1 month, 3 months, 6 months, 1 year, and 2 years after surgery. Only urine samples of esophageal cancer patients who underwent preoperative chemotherapy were additionally collected right after the completion of preoperative chemotherapy
Fig. 3
Fig. 3
The chart of exclusion criteria in this study. Sixty patients were initially enrolled in this study; 20 were excluded based on exclusion criteria. The remaining 40 patients included. Of these, 32 patients were followed up for 2 years after surgery
Fig. 4
Fig. 4
Box plots of chemotaxis responses from recurrence and non-recurrence patients. Analysis using chemotaxis indexes of urine samples of 28 cases with vascular invasion including 5 recurrence and 23 non-recurrence patients showed a significant association of chemotaxis index and recurrence
Fig. 5
Fig. 5
ROC analysis of 28 cases with vascular invasion. The ROC analysis based on chemotaxis index (1st sample) with 100-fold diluted urines of 28 vascular invasion cases showed a high AUC value
Fig. 6
Fig. 6
The surveillance follow-up on recurrence cases with N-NOSE. The chemotaxis indexes of seven recurrence cases were monitored at pre-operation, post-operation, before recurrence, and after therapy for recurrence. Five cases, patients #34, 36, 37, 38, and 39 showed similar trends with 10- or 100-fold diluted urine samples, where the positive index of pre-operation samples reduced at post-operation, slightly increased before the recurrence, and three of these patients (#34, 38, and 39) who showed treatment response again dropped after therapy for recurrence
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