Fusobacterium nucleatum as a prognostic marker of colorectal cancer in a Japanese population

Yamaoka, Y.; Suehiro, Yutaka; Hashimoto, Shinichi; Hoshida, Tomomi; Fujimoto, Michiyo; Watanabe, Moriyoshi; Imanaga, Daiki; Sakai, Kazuhisa; Matsumoto, Toshihiko; Nishioka, Michio; Takami, Taro; Suzuki, Nobuaki; Hazama, Shoichi; Nagano, Hiroaki; Sakaida, Isao; Yamasaki, Takahiro

doi:10.1007/s00535-017-1382-6

Cited by 118 publications

(117 citation statements)

References 36 publications

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“…Fusobacterium nucleatum numbers are significantly correlated with tumor size, and shortened survival times in a population of human Japanese patients with later stage CRC compared to earlier stages 53. These findings, as well as additional observations in rodent models and humans with CRC suggest that chronic inflammatory disease of the GI tract is a potential risk factor for the development of additional channels for amplified inflammatory processes, aneuploidy, high‐grade dysplasia, metaplasia and loss of cellular proliferative checkpoints, all of which are processes that can be appreciated in malignancy 13, 19, 54, 58, 59.…”

Section: Discussionmentioning

confidence: 99%

“…This probe array was selected to identify specific bacterial groups and individual bacterial species previously shown to be relevant in the pathogenesis of intestinal cancers in humans, rodents, and dogs. 9,14,19,22,23,27,[35][36][37][38][39][40][41][42][43][44][45][46][47][48][49][50][51][52][53][54] Tissue sections were bathed in 30μL of DNA-probe-hybridization buffer mix in a hybridization chamber maintained at 54 C overnight (12 hours). Buffer 1 (20mM Tris, 0.9M NaCl, 0.1% SDS, 20% Formamide, 10% Dextran sulfate) was used for the hybridization of Eub338, Erec482, Bacto1080, Fuso0664, Ebac1790 and Faecali698.…”

Section: Fluorescence In Situ Hybridization (Fish)mentioning

confidence: 99%

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Relationship of the mucosal microbiota to gastrointestinal inflammation and small cell intestinal lymphoma in cats

Garraway

Johannes

Bryan

et al. 2018

Veterinary Internal Medicne

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BackgroundThe gastrointestinal (GI) microbiota in healthy cats is altered in IBD. Little research has been performed to identify whether specific bacterial groups are associated with small cell GI lymphoma (LSA).HypothesisMucosal bacteria, including Enterobacteriaceae and Fusobacterium spp., are abundant in intestinal biopsies of cats with small cell GI LSA compared to cats with IBD.AnimalsFourteen cats with IBD and 14 cats with small cell GI LSA.MethodsRetrospective case control study. A search of the medical records was performed to identify cats diagnosed with IBD and with GI LSA. Bacterial groups identified by FISH in GI biopsies were compared between cohorts and correlated to CD11b+ and NF‐κB expression.Results Fusobacterium spp. (median; IQR bacteria/region) were higher in cats with small cell GI LSA in ileal (527; 455.5 – 661.5; P = .046) and colonic (404.5; 328.8 – 455.5; P = .016) adherent mucus, and combined colonic compartments (free mucus, adherent mucus, attaching to epithelium) (8; 0 – 336; P = .017) compared to cats with IBD (ileum: 67; 31.5 – 259; colon: 142.5; 82.3 – 434.5; combined: 3; 0 – 34). Bacteroides spp. were higher in ileal adherent mucus (P = .036) and 3 combined ileal compartments (P = .034) of cats with small cell GI LSA. There were significant correlations between Fusobacterium spp. totals and CD11b+ cell (P = .009; rs .476) and NF‐κB expression (P = .004; rs .523).ConclusionsThe bacterial alterations appreciated might be influential in development of small cell GI LSA, and should drive further studies to elucidate the effects of microbial‐mediated inflammation on GI cancer progression.

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Section: Discussionmentioning

confidence: 99%

Section: Fluorescence In Situ Hybridization (Fish)mentioning

confidence: 99%

Relationship of the mucosal microbiota to gastrointestinal inflammation and small cell intestinal lymphoma in cats

Garraway

Johannes

Bryan

et al. 2018

Veterinary Internal Medicne

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“…It has been reported that the accumulation of F. nucleatum in colorectal tumor is partly due to fusobacterial lectin Fap2 and FadA adhesin and that F. nucleatum can induce the carcinogenesis and development of colorectal tumor by the microRNA‐21‐mediated pathway or inhibition of host adaptive immunity, etc Recently, our group also found that F. nucleatum promoted chemoresistance by modulating autophagy in CRC . F. nucleatum was reported to be associated with the prognosis of CRC as well . There also have been some studies exploring diagnosing colorectal tumor with F. nucleatum from tumor tissues or feces.…”

Section: Discussionmentioning

confidence: 99%

Fecal Fusobacterium nucleatum for the diagnosis of colorectal tumor: A systematic review and meta‐analysis

et al. 2019

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The fecal Fusobacterium nucleatum has been reported as a potential noninvasive biomarker for colorectal tumor in several studies, but its exact diagnostic accuracy was ambiguous due to the wide range of sensitivity and specificity. To assess the diagnostic accuracy of fecal F. nucleatum for colorectal tumor, we searched electronic databases including PubMed, Cochrane Library, Embase, and Web of Science, without any date and language restrictions. Two reviewers independently extracted data and appraised study quality with Quality Assessment of Diagnostic Accuracy Studies. We included ten studies comprising 13 cohorts for colorectal cancer (CRC) and seven cohorts for colorectal adenoma (CRA). A total of 1450 patients and 1421 controls for CRC and 656 patients and 827 controls for CRA were included. The pooled sensitivity and specificity of fecal F. nucleatum for CRC were 71% (95% CI, 61%‐79%) and 76% (95% CI, 66%‐84%), with the area under the receiver‐operating characteristics (AUC) curve of 0.80 (95% CI, 0.76‐0.83). The pooled sensitivity and specificity of fecal F. nucleatum for CRA were 36% (95% CI, 27%‐46%) and 73% (95% CI, 65%‐79%), with an AUC of 0.60 (95% CI, 0.56‐0.65). Substantial heterogeneity among studies existed, which was partly caused by DNA extraction kits, regions of study, sample size, and demographic characteristics of participants. Fecal F. nucleatum was valuable for the diagnosis of CRC although it performed below expectation. For CRA, the specificity of fecal F. nucleatum indicated the possibility of noninvasive screening. Subgroup analyses for adenoma were incomplete due to lack of data. Heterogeneity limited the credibility of the study.

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“…The most commonly used test method for F.nucleatum was quantitative polymerase chain reaction(qPCR), 8,[12][13][14][15][18][19][20][21] besides, three studies 9,11,16 used the 16S ribosomal RNA(16sRNA) and Yuko Yamaoka used droplet digital PCR. 17 All patients described in the retrieved articles were divided into two groups based on high or low expression of F.nucleatum DNA.…”

Section: Flow Diagram Of the Studies Retrieved For The Reviewmentioning

confidence: 99%

“…In this analysis, F.nucleatum enrichment was signi cantly associated with poor CSS (HR = 1.93, 95% CI: 1.42-2.62 P < 0.0001) through the application of the xed-effects model, with low heterogeneity (I 2 = 0%, P = 0.69). ( Table 2, data from eleven articles 8,[11][12][13][14][15][16][17][18][19]21 for a total of 3413 patients were selected for analysis of the association between the abundance of F.nucleatum and primary tumor site in a randomeffects model (I 2 = 60%, P = 0.005). The result suggested that there is no signi cance evidence proving the correlation between F.nucleatum infection and tumor site (OR = 1.26, 95% CI: 0.91-1.75, P = 0.17) ( supplemental Fig.…”

Section: Association Between Fnucleatum Abundance and Prognosis Of Cmentioning

confidence: 99%

Clinicopathological and prognostic significance of Fusobacterium nucleatum infection in colorectal cancer: a meta-analysis

Huangfu

Zhang

Zhang³

et al. 2020

Preprint

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Background: Accumulating evidences about the association between Fusobacterium nucleatum (F. nucleatum) and colorectal cancer (CRC) has been reported in various studies. However, the definite relationship between abundance of F. nucleatum with clinical characteristics and prognosis of CRC is still controversial. Methods: PubMed, Embase and Web of Science were searched for relevant articles up to April 7, 2020. Outcomes of interest included clinical characteristics, molecular characteristic and survival analysis. HR (OR), odds ratios (OR) and 95% confidence interval (CI) were calculated to explore the prognostic value and relationship of clinical characteristics of Fusobacterium nucleatum in CRC.Results: A total of 3626 patients with CRC from 13 eligible studies were included. High abundance of F. nucleatum was associated with worse prognosis on overall survival (OS) (HR= 1.40, P < 0.0001), disease-free survival (DFS) (HR = 1.71, P = 0.0002) and cancer-specific survival (OR= 1.93, P <0.0001). In addition, F. nucleatum abundance was related with T (T3-T4) stage(OR = 2.20, P < 0.00001), M (M1) stage (OR = 2.11, P = 0.005), poor tumor differentation(OR = 1.83, P =0.02), microsatellite instability (MSI) -high (OR = 2.53, P = 0.0003) and KRAS mutation (OR =1.27, P=0.05).Conclusion: The present evidences revealed that high abundance of F. nucleatum is inclined to indicate worse prognosis and is associated with tumor growth, distant Impact: This study highlights the risk factor of F. nucleatum for worse prognosis of CRC.

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Fusobacterium nucleatum as a prognostic marker of colorectal cancer in a Japanese population

Abstract: These results suggest that determining F. nucleatum levels may help predict clinical outcomes in colorectal cancer patients. Further confirmatory studies using independent datasets are required to confirm our findings.

Cited by 118 publications

References 36 publications

Relationship of the mucosal microbiota to gastrointestinal inflammation and small cell intestinal lymphoma in cats

Relationship of the mucosal microbiota to gastrointestinal inflammation and small cell intestinal lymphoma in cats

Fecal Fusobacterium nucleatum for the diagnosis of colorectal tumor: A systematic review and meta‐analysis

Clinicopathological and prognostic significance of Fusobacterium nucleatum infection in colorectal cancer: a meta-analysis

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