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

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.

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

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

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

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

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

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