Highly sensitive stool DNA testing of <i>Fusobacterium nucleatum</i> as a marker for detection of colorectal tumours in a Japanese population

Suehiro, Yutaka; Sakai, Kazuhisa; Nishioka, Michio; Hashimoto, Shinichi; Takami, Taro; Higaki, Shingo; Shindo, Yoshitaro; Hazama, Shoichi; Oka, M.; Nagano, Hiroaki; Sakaida, Isao; Yamasaki, Takahiro

doi:10.1177/0004563216643970

Cited by 63 publications

(73 citation statements)

References 33 publications

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“…A significantly increased relative abundance of Fn was detected in adenoma patients as compared with healthy controls [7.1e À5 (4.8e À6 -0.0007) vs. 8.1e À6 (0-0.0004), median (IQR); P < 0.05], which is consistent with the previous finding by Suehiro and colleagues in Japanese population (25). Fn alone gave an AUROC of 0.609 (0.545-0.674; P < 0.05) in discriminating adenoma patients from control subjects.…”

Section: Discussionsupporting

confidence: 91%

Fecal Bacteria Act as Novel Biomarkers for Noninvasive Diagnosis of Colorectal Cancer

Liang

Chiu

Chen

et al. 2017

Clinical Cancer Research

257

251

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Purpose: Gut microbiota have been implicated in the development of colorectal cancer. We evaluated the utility of fecal bacterial marker candidates identified by our metagenome sequencing analysis for colorectal cancer diagnosis.Experimental Design: Subjects (total 439; 203 colorectal cancer and 236 healthy subjects) from two independent Asian cohorts were included. Probe-based duplex quantitative PCR (qPCR) assays were established for the quantification of bacterial marker candidates.Results: Candidates identified by metagenome sequencing, including Fusobacterium nucleatum (Fn), Bacteroides clarus (Bc), Roseburia intestinalis (Ri), Clostridium hathewayi (Ch), and one undefined species (labeled as m7), were examined in fecal samples of 203 colorectal cancer patients and 236 healthy controls by duplex-qPCR. Strong positive correlations were demonstrated between the quantification of each candidate by our qPCR assays and metagenomics approach (r ¼ 0.801-0.934, all P < 0.0001). Fn was significantly more abundant in colorectal cancer than controls (P < 0.0001), with AUROC of 0.868 (P < 0.0001). At the best cut-off value maximizing sum of sensitivity and specificity, Fn discriminated colorectal cancer from controls with a sensitivity of 77.7%, and specificity of 79.5% in cohort I. A simple linear combination of four bacteria (Fn þ Ch þ m7-Bc) showed an improved diagnostic ability compared with Fn alone (AUROC ¼ 0.886, P < 0.0001) in cohort I. These findings were further confirmed in an independent cohort II. In particular, improved diagnostic performances of Fn alone (sensitivity 92.8%, specificity 79.8%) and four bacteria (sensitivity 92.8%, specificity 81.5%) were achieved in combination with fecal immunochemical testing for the detection of colorectal cancer.Conclusions: Stool-based colorectal cancer-associated bacteria can serve as novel noninvasive diagnostic biomarkers for colorectal cancer.

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Section: Discussionsupporting

confidence: 91%

Fecal Bacteria Act as Novel Biomarkers for Noninvasive Diagnosis of Colorectal Cancer

Liang

Chiu

Chen

et al. 2017

Clinical Cancer Research

257

251

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“…For cohorts with larger sample size (>200), the diagnostic ability of fecal F. nucleatum for CRC was better than cohorts with smaller sample size, with lower sensitivity. And the heterogeneity of sensitivity, positive DLR, and negative DLR all dropped sharply.…”

Section: Resultsmentioning

confidence: 95%

“…The results of the QADAS‐2 for CRC and CRA are shown in Figure and Table , indicating that highest risk of bias existed in “patient selection” and “index text.” The former one is because that all of the included studies were case‐control study and the percentage of colorectal tumor patients in all subjects was inconsistent with its prevalence rate. However, except for the one that did not mention the way of subject selection, the other studies all recruited participants consecutively or randomly. The latter one is caused by cutoff values not being determined beforehand in all studies but one .…”

Section: Resultsmentioning

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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“…Our findings allowed us to identify bacteria that are found both in higher and lower RA in invasive cancer patients compared to early cancer patients. The initial finding of significant higher Fusobacterium genus in both colon and feces gives support to the studies that used Fusobacterium fecal tests for CRC . However, the p value for such difference in fecal samples differed greatly from the brush samples ( P = 0.05 and P < .0001, respectively – Supporting information table S1).…”

Section: Discussionmentioning

confidence: 61%

“…The initial finding of significant higher Fusobacterium genus in both colon and feces gives support to the studies that used Fusobacterium fecal tests for CRC. 14,15 However, the p value for such difference in fecal samples differed greatly from the brush samples (P = 0.05 and P < .0001, respectively -Supporting information table S1). In addition, we could only isolate some difference in species when looking at colon samples.…”

Section: Discussionmentioning

confidence: 95%

Microbiota profile is different for early and invasive colorectal cancer and is consistent throughout the colon

Yamamoto

Honda

et al. 2019

J of Gastro and Hepatol

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Background and Aim Microbiota have been associated with several diseases including colorectal cancer (CRC). This study aimed to evaluate the microbiota in early/invasive CRC utilizing stool and cytological brushes to determine differences in relative abundance (RA). Methods Colonoscopy patients referred for endoscopic submucosal dissection or previous to CRC surgery were prospectively enrolled. Stool was collected pre‐bowel preparation; and brush samples were taken during colonoscopy (three regions). DNA extraction, 16S rRNA next generation sequencing, and biostatistics (qiime and stamp software packages) followed. Primary outcome was the difference in RA of the Fusobacterium genus between the groups. Secondary outcomes included analyses of other microbiota. Results Twenty‐five patients were included, of which 14 had invasive cancer (≥ 1000 mm into the submucosa). The three major genera for invasive cancer were Bacterioides, Oribacterium, and Fusobacterium, whereas for early cancer were Oribacterium, Bacterioides, and Prevotella (decreasing order of RA). There was a significantly higher RA of Fusobacterium in the invasive cancer group (9.65% vs 0.95%, respectively, P < 0.001). The RA of all genera was similar throughout the colon. In addition to Fusobacterium, the genera Corynebacterium, Enterococcus, Neisseria, Porphyromonas, and Sclegelella showed statistically higher RA in the invasive cancer group. Conversely, the genera Oribacterium, Desulfovibrio, Clostridiales, and Lactobacillus showed lower RA in the invasive cancer group. Conclusions The RA of Fusobacterium is higher with invasive CRC than in early CRC patients. In addition, five other bacteria genera were found to be increased, and four decreased in invasive CRC patients. The microbiota per patient was similar throughout the colon.

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Highly sensitive stool DNA testing of Fusobacterium nucleatum as a marker for detection of colorectal tumours in a Japanese population

Cited by 63 publications

References 33 publications

Fecal Bacteria Act as Novel Biomarkers for Noninvasive Diagnosis of Colorectal Cancer

Fecal Bacteria Act as Novel Biomarkers for Noninvasive Diagnosis of Colorectal Cancer

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

Microbiota profile is different for early and invasive colorectal cancer and is consistent throughout the colon

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