Heterogeneous distribution of Fusobacterium nucleatum in the progression of colorectal cancer

Abstract

Background and Aim: Fusobacterium nucleatum (Fn) is involved in colorectal cancer (CRC) growth and is a biomarker for patient prognosis and management. However, the ecology of Fn in CRC and the distribution of intratumoral Fn are unknown. Methods: We evaluated Fn and the status of KRAS and BRAF in 200 colorectal neoplasms (118 adenomas and 82 cancers) and 149 matched adjacent normal mucosas. The differentiation status between "surface" and "deep" areas of cancer tissue and matched normal mucosa were analyzed in 46 surgical samples; the Ki-67 index was also evaluated in these samples. Results: Fusobacterium nucleatum presence in the tumor increased according to pathological stage (5.9% [adenoma] to 81.8% [stage III/IV]), while Fn presence in normal mucosa also increased (7.6% [adenoma] to 40.9% [stage III/IV]). The detection rates of Fn on the tumor surface and in deep areas were 45.7% and 32.6%, while that of normal mucosa were 26.1% and 23.9%, respectively. Stage III/IV tumors showed high Fn surface area expression (66.7%). Fn intratumoral heterogeneity (34.8%) was higher than that of KRAS (4.3%; P < 0.001) and BRAF (2.2%; P < 0.001). The Ki-67 index in Fn-positive cases was higher than that in negative cases (93.9% vs 89.0%; P = 0.01). Conclusions: Fusobacterium nucleatum was strongly present in CRC superficial areas at stage III/IV. The presence of Fn in the deep areas of adjacent normal mucosa also increased. The intratumoral heterogeneity of Fn is important in the use of Fn as a biomarker, as Fn is associated with CRC proliferative capacity.

Evaluating the presence of Mycoplasma hyorhinis, Fusobacterium nucleatum, and Helicobacter pylori in biopsies of patients with gastric cancer

“…In our study, the presence of F. nucleatum was significant at tumour size > 4 cm ( P = 0.053). Tumour size and TNM stage III/IV have also been associated with F. nucleatum in other studies [ 67 ]. In addition to FadA mechanisms, TLR4 activation by F. nucleatum ’ LPS can plausible lead to the activation of Myd88 and NF-κB, which leads to oncogenic overexpression of miR21, resulting in dysregulated growth and infiltration of tumour tissue.…”

Salivary Fusobacterium nucleatum serves as a potential biomarker for colorectal cancer

“…It has also been reported that Fn may encode virulence factors, such as FadA, Fap2, and MORN2 proteins, to induce CRC development ( Ranjbar et al., 2021 ). Consistent with these lines of experimental evidence, clinical studies demonstrate that the abundance of Fn in CRC tissues is significantly increased compared with the adjacent normal tissues, and a high prevalence of Fn is associated with advanced stage, metastasis, recurrence, and short OS of CRC patients ( Eisele et al., 2021 ; Mima et al., 2016 ; Serna et al., 2020 ; Yamamoto et al., 2021 ).Therefore, Fn, as a potential oncobacterium, may be helpful for the early detection and prognostic prediction of CRC.…”

The Impact of KRAS Mutation in Patients With Sporadic Nonampullary Duodenal Epithelial Tumors

“…The importance of Fn in colorectal tumors has recently been revealed. We have previously reported the presence of Fn in colorectal adenoma and colorectal cancer ( 20 ), and we hypothesized that Fn might play an important role in SNADETs as well. The incidence of Fn in duodenal adenoma, early-stage duodenal adenocarcinoma, and advanced-stage duodenal adenocarcinoma was 10.9%, 24.4%, and 25.0%, respectively ( P = 0.10).…”

“…The amount of Fn DNA in tissues was measured by qPCR. Custom-made primer/probe sets were used to amplify Fn and the reference human gene solute carrier organic anion transporter family number 2A1 ( SLCO2A1 ), as previously described ( 20 ). The primer and probe sequences are summarized in Supplemental Table 1 (Supplementary Digital Content 1, http://links.lww.com/CTG/A718 ).…”