Fusobacterium nucleatumin colorectal carcinoma tissue and patient prognosis

Abstract

Objective Accumulating evidence links the intestinal microbiota and colorectal carcinogenesis. Fusobacterium nucleatum may promote colorectal tumour growth and inhibit T-cell-mediated immune responses against colorectal tumours. Thus, we hypothesized that the amount of Fusobacterium nucleatum in colorectal carcinoma might be associated with worse clinical outcome. Design We utilised molecular pathological epidemiology database of 1,069 rectal and colon cancer cases in the Nurses’ Health Study and the Health Professionals Follow-up Study, and measured Fusobacterium nucleatum DNA in carcinoma tissue. Cox proportional hazards model was used to compute hazard ratio (HR), controlling for potential confounders, including microsatellite instability (MSI, mismatch repair deficiency), CpG island methylator phenotype (CIMP), KRAS, BRAF, and PIK3CA mutations, and LINE-1 hypomethylation (low-level methylation). Results Compared to Fusobacterium nucleatum-negative cases, multivariable HRs (95% confidence interval) for colorectal cancer-specific mortality in Fusobacterium nucleatum-low cases and Fusobacterium nucleatum-high cases were 1.25 (0.82 to 1.92) and 1.58 (1.04 to 2.39), respectively (p for trend = 0.020). The amount of Fusobacterium nucleatum was associated with MSI-high (multivariable odds ratio, 5.22; 95% CI, 2.86 to 9.55) independent of CIMP and BRAF mutation status, whereas CIMP and BRAF mutation were associated with Fusobacterium nucleatum only in univariate analyses (p < 0.001) but not in multivariate analysis that adjusted for MSI status. Conclusions The amount of Fusobacterium nucleatum DNA in colorectal cancer tissue is associated with shorter survival, and may potentially serve as a prognostic biomarker. Our data may have implications in developing cancer prevention and treatment strategies through targeting gastrointestinal microflora by diet, probiotics, and antibiotics.

Expression of DNA methyltransferases and target microRNAs in human tissue samples related to sporadic colorectal cancer

“…During the past decade, an emerging notion that the contributions of the TME to carcinogenesis must be considered in the biology of neoplasms (16), revealing an important role of local tissue microenvironment involving in the formation of tumor-associated stroma in tumorigenesis. To date, several studies have found that altered tissue microenvironment has an effect on colorectal carcinogenesis, and epigenetic changes function as a key player in cellular response to the alteration of microenvironment (46)(47)(48), which are consistent with our results revealing the histologically altered morphologies of tissues with different distance to CRC lesions, loss of normal crypts and existence of many ACf in no. 3, however, tissues no.…”

Gut microbiota modulate T cell trafficking into human colorectal cancer

“…Surprisingly, also bacterial species, such as Fusobacteria, reportedly associated with severe clinical outcome25 and that we found enriched in poorly infiltrated tumours, were capable to evoke expression of T cell recruiting chemokine genes by CRC cells in vitro. Further studies are warranted to clarify the final impact of individual bacterial species, and Fusobacteria in particular, on T cell function.…”

Fusobacterium nucleatum Promotes Chemoresistance to Colorectal Cancer by Modulating Autophagy

“…Two groups have recently shown that the abundance of F. nucleatum is gradually increased from normal tissues to adenoma tissues and to adenocarcinoma tissues in colorectal carcinogenesis (Castellarin et al, 2012; Kostic et al, 2012). Moreover, the amount of F. nucleatum in CRC tissues is associated with shorter survival (Mima et al, 2016). F. nucleatum adhesin FadA may bind to the E-cadherin protein and promote colorectal carcinogenesis (Rubinstein et al, 2013).…”