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

ABSTRACT: 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.

SUBMITTER: Zhang X

PROVIDER: S-EPMC6382715 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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

Zhang Xinyu X Zhu Xiaoqiang X Cao Yingying Y Fang Jing-Yuan JY Hong Jie J Chen Haoyan H

Cancer medicine 20190112 2

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 ap ...[more]

PMID: 30636375

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Project description:BackgroundDespite a considerable amount of epidemiological research for identification of risk factors involved in the development of colorectal cancer, the current understanding of the etiology of this disease remains rather poor. Accumulating evidence suggests a potentially important role of infection with Fusobacterium nucleatum in the colon in colorectal carcinogenesis. The objective of this systematic review is to synthesize the epidemiological evidence on the association between infection with Fusobacterium nucleatum in the colon and colorectal cancer.MethodsThis systematic review will include observational studies (cohort, case-control, cross-sectional) in humans in which the role of Fusobacterium nucleatum in the etiology of colorectal cancer was investigated. MEDLINE, EMBASE, Web of Science, and Cochrane Database of Systematic Reviews will be searched using a comprehensive search strategy and manual screening of references. Two reviewers will independently identify eligible studies and extract the data from the included studies. The quality of studies will be assessed by using the Newcastle-Ottawa scale. Random-effects models will be used to estimate pooled measures of association (where feasible). Meta-regression and subgroup analyses will be conducted to explore the potential sources of heterogeneity. The Meta-Analysis of Observational Studies in Epidemiology (MOOSE) guidelines and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement will be followed for reporting.DiscussionDeepening knowledge regarding the etiology of colorectal cancer and the potential implications of Fusobacterium nucleatum in this disease is instrumental for prevention, diagnosis, and treatment of this often-fatal disease. This review will produce summarized current evidence on this topic.Systematic review registrationThis systematic review protocol has been registered with the International Prospective Register of Systematic Reviews (PROSPERO) on 10 July 2018 (registration number CRD42018095866).

Project description:ImportanceEvidence indicates a complex link between gut microbiome, immunity, and intestinal tumorigenesis. To target the microbiota and immunity for colorectal cancer prevention and therapy, a better understanding of the relationship between microorganisms and immune cells in the tumor microenvironment is needed. Experimental evidence suggests that Fusobacterium nucleatum may promote colonic neoplasia development by downregulating antitumor T cell-mediated adaptive immunity.ObjectiveTo test the hypothesis that a greater amount of F nucleatum in colorectal carcinoma tissue is associated with a lower density of T cells in tumor tissue.Design, setting, and participantsA cross-sectional analysis was conducted on 598 rectal and colon carcinoma cases in 2 US nationwide prospective cohort studies with follow-up through 2006, the Nurses' Health Study (participants enrolled in 1976) and the Health Professionals Follow-up Study (participants enrolled in 1986). Tissue collection and processing were performed from 2002 through 2008, and immunity assessment, 2008 through 2009. From 2013 through 2014, the amount of F nucleatum in colorectal carcinoma tissue was measured by quantitative polymerase chain reaction assay; we equally dichotomized positive cases (high vs low). Multivariable ordinal logistic regression analysis was conducted in 2014 to assess associations of the amount of F nucleatum with densities (quartiles) of T cells in tumor tissue, controlling for clinical and tumor molecular features, including microsatellite instability, CpG island methylator phenotype, long interspersed nucleotide element-1 (LINE-1) methylation, and KRAS, BRAF, and PIK3CA mutation status. We adjusted the 2-sided α level to .013 for multiple hypothesis testing.Main outcomes and measuresDensities of CD3+, CD8+, CD45RO (protein tyrosine phosphatase receptor type C [PTPRC])+, and FOXP3+ T cells in tumor tissue, determined by means of tissue microarray immunohistochemical analysis and computer-assisted image analysis.ResultsF nucleatum was detected in colorectal carcinoma tissue in 76 (13%) of 598 cases. Compared with F nucleatum-negative cases, F nucleatum-high cases were inversely associated with the density of CD3+ T cells (for a unit increase in quartile categories of CD3+ T cells as an outcome: multivariable odds ratio, 0.47 [95% CI, 0.26-0.87]; P for trend = .006). The amount of F nucleatum was not significantly associated with the density of CD8+, CD45RO+, or FOXP3+ T cells (P fortrend = .24, .88, and .014, respectively).Conclusions and relevanceThe amount of tissue F nucleatum is inversely associated with CD3+ T-cell density in colorectal carcinoma tissue. On validation, our human population data may provide an impetus for further investigations on potential interactive roles of Fusobacterium and host immunity in colon carcinogenesis.

Dataset Information

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

Publications

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

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