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

ABSTRACT: Background: This study aimed to clarify the relationship between F. nucleatum levels and the prognosis of CRC, which is still controversial. Methods: Relevant articles were searched on PubMed, Web of Science, PMC and Embase 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 CRC patients from 13 eligible studies were included. High levels of F. nucleatum were associated with worse prognosis, as such parameters as overall survival (OS) (hazard ratio [HR] = 1.40, 95% confidence interval [CI]: 1.40 - 1.63, P < 0.0001), disease-free survival (DFS) (HR = 1.71, 95% CI: 1.29-2.26, P = 0.0002), and cancer-specific survival (OR= 1.93, 95% CI: 1.42-2.62, P <0.0001). F. nucleatum levels were related with T3-T4 stage (OR = 2.20, 95% CI: 1.66-2.91, P < 0.00001), M1 stage (OR = 2.11, 95% CI: 1.25-3.56, P = 0.005), poor tumor differentiation (OR = 1.83, 95% CI: 1.11-3.03, P =0.02), microsatellite instability-high (OR = 2.53, 95% CI: 1.53-4.20, P = 0.0003), and KRAS mutation (OR =1.27, 95% CI: 1.00-1.61, P=0.05) showed. Conclusions: High levels of F. nucleatum suggest a poor prognosis and are associated with tumor growth, distant metastasis, poor differentiation, MSI-high, and KRAS mutation in CRC patients.

SUBMITTER: Huangfu SC

PROVIDER: S-EPMC7890333 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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

Huangfu Shu-Chen SC Zhang Wen-Bin WB Zhang Hao-Ran HR Li Yang Y Zhang Yi-Ran YR Nie Jin-Lin JL Chu Xiao-Dong XD Chen Chang-Shun CS Jiang Hai-Ping HP Pan Jing-Hua JH

Journal of Cancer 20210115 6

<b>Background:</b> This study aimed to clarify the relationship between F. nucleatum levels and the prognosis of CRC, which is still controversial. <b>Methods:</b> Relevant articles were searched on PubMed, Web of Science, PMC and Embase 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 c ...[more]

PMID: 33613745

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Project description:ObjectiveTo systematically evaluate the significance of Fusobacterium nucleatum (Fn) levels the clinicopathological impacts of cancer.MethodsLiterature from Pubmed, Embase, and Web of Science was retrieved to collect all English literatures on the correlation between Fn and cancer, and the quality of literatures collected was assessed based on the Newcastle-Ottawa Quality Assessment Scale. The heterogeneity and sensitivity were detected by Stata 14.0 software, and the correlation between Fn and cancer clinicopathological as the effect variables was assessed according to the odds ratio (OR) and 95% confidence interval (CI). The forest plot was drawn.ResultsA total of 19 articles meeting the inclusion criteria were selected. The incidence of Fn prevalence varied considerably (range: 6.1 to 83.3%) and was greater than 10% in 13 of 19 studies. Compared with those with no/low Fn levels, the high levels of Fn was positively associated with vascular invasion, nerve invasion, depth of invasion, and distant metastasis [vascular invasion: OR = 1.66, 95%CI(1.07, 2.57), I 2 = 21.9%, fixed effect model; nerve invasion: OR = 1.36, 95%CI(1.00, 1.84), I 2 = 43.1%, fixed effect model; infiltration depth: OR = 1.94, 95%CI(1.20, 3.15), I 2 = 67.2%, random effect model; distant metastasis: OR = 1.80, 95%CI(1.23, 2.64), I 2 = 3.4%, fixed effect model]. Patients with MLH1 methylation always present a higher Fn levels than those without methylation [OR = 2.53, 95%CI(1.42, 4.53), P = 0.01, I 2 = 57.5%, random effect model]. Further, Fn was associatedwith the molecular characteristics of cancers [MSI-H Vs. MSS/MSI-low: OR = 2.92, 95%CI(1.61, 5.32), P = 0.01, I 2 = 63.2%, random effect model; High Vs. Low/Negative CIMP: OR = 2.23, 95%CI(1.64, 3.03), P = 0.01, I 2 = 64.2%, random effect model; KRAS mutation Vs. wild-type: OR = 1.24, 95%CI(1.04, 1.48), P = 0.02, I 2 = 27.0%, fixed effect model; Present Vs. Abscent BRAF mutations: OR = 1.88, 95%CI(1.44, 2.45), P = 0.01, I 2 = 24.2%, fixed effect model]. The cancer patients with high levels of Fn often have worse RFS than those with no/low Fn levels[OR = 1.14, 95%CI(0.61, 1.68), P = 0.01, I 2 = 80.7%, random effect model].ConclusionThis review and meta-analysis showed that Fn could be used to predict unfavorable prognosis and function as potential prognostic biomarkers in colorectal cancer (CRC). Our data may have implications for targeting Fn to develop strategies for cancer prevention and treatment.

Project description:Objective:To assess the association between MUC expression levels in colorectal cancer (CRC) tissues and prognosis and investigate the associations between MUC expression levels and CRC clinicopathological characteristics. Methods:The PubMed, Embase, Cochrane Library, and Web of Science databases were searched from inception through September 13, 2019, to identify studies investigating the association between MUC expression levels in CRC tissues and prognosis. Pooled hazard ratios (HRs) or odds ratio (ORs) with 95% confidence intervals (CIs) were used to evaluate associations between MUC expression levels and prognosis or clinicopathological characteristics, respectively. The heterogeneity between studies was assessed by the I 2 values, whereas the likelihood of publication bias was assessed by Egger's linear regression and Begg's rank correlation test. Results:Among 33 included studies (n = 6032 patients), there were no associations between combined MUC phenotype expression levels and overall survival (OS) or disease-free survival (DFS)/relapse-free survival (RFS) in patients with CRC. In subgroup analyses, the upregulated MUC1 expression (HR = 1.50; 95% CI, 1.29-1.74; P < 0.00001) was associated with poor OS. However, the upregulated MUC2 expression (HR = 0.64; 95% CI, 0.52-0.79; P < 0.00001) was associated with better OS. Furthermore, a high level of MUC1 expression (HR = 1.99; 95% CI, 0.99-3.99; P = 0.05) was associated with shorter DFS/RFS. However, patients with a low level of MUC2 tumors showed better DFS/RFS than patients with a high level of MUC2 tumors (HR = 0.71; 95% CI, 0.49-1.04; P = 0.08; P = 0.0.009, I 2 = 67%) and MUC5AC expression (HR = 0.56; 95% CI, 0.38-0.82; P = 0.003) was associated with longer DFS/RFS. In addition, a high level of MUC1 expression was associated with CRC in the rectum, deeper invasion, lymph node metastasis, distant metastasis, advanced tumor stage, and lymphatic invasion. A high level of MUC2 expression had a protective effect. High secretion of MUC5AC is associated with colon cancer compared with rectal cancer. Conclusion:The protein expression of MUC1 might be a poor biomarker in colorectal cancer and might play a role in tumor transformation and metastasis. However, the protein expression of MUC2 expression might have a protective effect. Furthermore, randomized controlled trials (RCTs) of large patients are needed to confirm the results.

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).

Dataset Information

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

Publications

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

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