Abstract

Fusobacterium nucleatum (F. nucleatum) is frequently detected in primary colorectal cancer (CRC) and matching metastasis, and has been linked to a worse prognosis. We investigated the presence of F. nucleatum in gastric cancer (GC) and gastric preneoplastic conditions of the stomach, and its potential prognostic value in GC patients. Fusobacterium spp. and F. nucleatum were quantified in various specimens from gastrointestinal tract including paired CRC and GC tissues using probe-based qPCR. Fusobacterium spp. and F. nucleatum were more frequently found in tumorous tissue of CRC and GC compared to non-tumorous tissues. The frequency and bacterial load were higher in CRC compared to GC patients. F. nucleatum positivity showed no association to chronic gastritis or preneoplastic conditions such as intestinal metaplasia. F. nucleatum-positivity was associated with significantly worse overall survival in patients with Lauren’s diffuse type, but not with intestinal type GC. There was no association with gender, Helicobacter pylori-status, tumor stage or tumor localization. However, F. nucleatum was positively associated with patient’s age and a trend for a lower global long interspersed element-1 DNA methylation. In conclusion, our work provides novel evidence for clinical relevance of F. nucleatum in GC by showing an association between F. nucleatum positivity with worse prognosis of patients with Laurens’s diffuse type gastric cancer. Further studies are necessary to explore related mechanistic insights and potential therapeutic benefit of targeted antibiotic treatment in GC patients.

Highlights

  • Fusobacterium nucleatum (F. nucleatum) is frequently detected in primary colorectal cancer (CRC) and matching metastasis, and has been linked to a worse prognosis

  • We confirm that Fusobacterium spp. and F. nucleatum are more frequently detectable in T-CRC than in N-CRC and F. nucleatum load correlates significantly between tumorous and nontumorous tissues

  • Only limited data is available on the role of F. nucleatum in gastric cancer (GC) and gastric preneoplastic conditions

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Summary

Introduction

Fusobacterium nucleatum (F. nucleatum) is frequently detected in primary colorectal cancer (CRC) and matching metastasis, and has been linked to a worse prognosis. Our work provides novel evidence for clinical relevance of F. nucleatum in GC by showing an association between F. nucleatum positivity with worse prognosis of patients with Laurens’s diffuse type gastric cancer. F. nucleatum is found in tumorous tissues at higher bacterial load in comparison to adjacent non-tumorous m­ ucosa[8,11]. It has been traced from primary tumours to liver metastases and was associated with a worse prognosis, suggesting its potential role in carcinogenesis and possible therapeutic translational ­implications[12]. F. nucleatum has been correlated with expression of proinflammatory genes, lower ­CD3+ T-cell density and increased TNF-α gene expression in CRC1​ 4–16

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