Fusobacterium nucleatum in the Colorectum and Its Association with Cancer Risk and Survival: A Systematic Review and Meta-analysis

Abstract

Background: The gut microbiome, in particular Fusobacterium nucleatum, has been reported to play a role in colorectal cancer development and in patient prognosis. We aimed to perform a systematic review and meta-analysis of published studies to assess the prevalence of F. nucleatum in colorectal tumors and evaluate the association between F. nucleatum and colorectal cancer development and prognosis.Methods: MEDLINE, EMBASE, and Web of Science databases were systematically searched for studies published until January 2019. Random effects meta-analyses were used to assess the prevalence of F. nucleatum in patients with colorectal cancer or tissues relative to controls and survival in F. nucleatum-positive versus -negative patients.Results: Forty-five relevant articles were identified. Meta-analyses indicated higher odds of F. nucleatum being present in colorectal tissue samples from patients with colorectal cancer [n ¼ 6 studies, pooled OR ¼ 10.06; 95% confidence intervals (CI), 4.48-22.58] and individuals with colorectal polyps (n ¼ 5 studies, pooled OR ¼ 1.83; 95% CI, 1.07-3.16) compared with healthy controls. Similar results were apparent in fecal samples, and when comparing tumor with adjacent normal tissue. Meta-analyses indicated poorer survival in patients with colorectal cancer with high versus low F. nucleatum abundance (n ¼ 5 studies, pooled HR ¼ 1.87; 95% CI, 1.12-3.11).Conclusions: A consistent increase in the prevalence and/or abundance of F. nucleatum in colorectal cancer tissue and fecal samples compared with controls was apparent. High abundance of F. nucleatum in colorectal tumors was also associated with poorer overall survival.Impact: F. nucleatum could be useful as a diagnostic and prognostic marker for colorectal cancer or as a treatment target. Materials and Methods Data sourcesAn a priori systematic search of the literature was performed in accordance with PRISMA guidelines (Supplementary Table S1; ref. 14

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

“…Our result cleared that high abundance of F. nucleatum is correlate with poor OS of CRC patients. This result is similar with the previous study, 23 which report that F. nucleatum positivity in tumor tissue was associated with poorer OS in CRC patient. However, they found F. nucleatum positivity was not associated with the DFS and CSS in CRC patient.…”

“…Although previous meta-analysis had reported the carcinogenesis and diagnostic value of F. nucleatum for CRC, as well as the prognosis of F. nucleatum in CRC with very little literatures. 22,23 To our best knowledge, this is the rst meta-analysis to demonstrated the role of F.nucleatum in clinical and molecular characteristics of CRC, and the most comprehensive meta-analysis to clarify the prognostic role of F.nucleatum in CRC.…”

Fusobacterium nucleatum infection correlates with two types of microsatellite alterations in colorectal cancer and triggers DNA damage

“…A total of 304 cases of unselected sporadic CRC from North Carolina [ 9 , 10 ] were analyzed for MSI-H, MSI-L and EMAST [ 11 , 12 ]. The amount of Fn DNA per nanogram of tumor tissue DNA was also determined by qPCR (see Additional file 1 : Additional Materials and Methods).…”

Analysis of differentially expressed genes in oral epithelial cells infected with Fusobacterium nucleatum for revealing genes associated with oral cancer

“…In recent years, F. nucleatum has garnered a lot of attention in the initiation and progression of various malignancies, especially in colorectal cancer (CRC), through modulation of inflammation and tumour‐related signalling pathways 3 . Based on a latest meta‐analysis, a consistent increase in the abundance of F. nucleatum in CRC tissues was observed and high abundance of F. nucleatum was associated with poorer overall survival 4 . F. nucleatum was also correlated with oral cancers, 5 and F. nucleatum levels were significantly elevated in oral squamous cell carcinoma (OSCC) tissues 6,7 .…”