AUTHOR=de Carvalho Ana Carolina , de Mattos Pereira Leandro , Datorre José Guilherme , dos Santos Wellington , Berardinelli Gustavo Noriz , Matsushita Marcus de Medeiros , Oliveira Marco Antonio , Durães Ronilson Oliveira , Guimarães Denise Peixoto , Reis Rui Manuel 

TITLE=Microbiota Profile and Impact of Fusobacterium nucleatum in Colorectal Cancer Patients of Barretos Cancer Hospital

JOURNAL=Frontiers in Oncology

VOLUME=9

YEAR=2019

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2019.00813

DOI=10.3389/fonc.2019.00813

ISSN=2234-943X

ABSTRACT=<p>Microbial diversity has been pointed out as a major factor in the development and progression of colorectal cancer (CRC). We sought to explore the richness and abundance of the microbial community of a series of colorectal tumor samples treated at Barretos Cancer Hospital, Brazil, through 16S rRNA sequencing. The presence and the impact of <italic>Fusobacterium nucleatum</italic> (<italic>Fn</italic>) DNA in CRC prognosis was further evaluated by qPCR in a series of 152 CRC cases. An enrichment for potentially oncogenic bacteria in CRC was observed, with <italic>Fusobacterium</italic> being the most abundant genus in the tumor tissue. In the validation dataset, <italic>Fn</italic> was detected in 35/152 (23.0%) of fresh-frozen tumor samples and in 6/57 (10.5%) of paired normal adjacent tissue, with higher levels in the tumor (<italic>p</italic> = 0.0033). <italic>Fn</italic> DNA in the tumor tissue was significantly associated with proximal tumors (<italic>p</italic> = 0.001), higher depth of invasion (<italic>p</italic> = 0.014), higher clinical stages (<italic>p</italic> = 0.033), poor differentiation (<italic>p</italic> = 0.011), MSI-positive status (<italic>p</italic> &lt; 0.0001), BRAF mutated tumors (<italic>p</italic> &lt; 0.0001), and the loss of expression of mismatch-repair proteins MLH1 (<italic>p</italic> &lt; 0.0001), MSH2 (<italic>p</italic> = 0.003), and PMS2 (<italic>p</italic> &lt; 0.0001). Moreover, the presence of <italic>Fn</italic> DNA in CRC tissue was also associated with a worse patient cancer-specific survival (69.9 vs. 82.2% in 5 years; <italic>p</italic> = 0.028) and overall survival (63.5 vs. 76.5%; <italic>p</italic> = 0.037). Here we report, for the first time, the association of <italic>F. nucleatum</italic> presence with important clinical and molecular features in a Brazilian cohort of CRC patients. Tumor detection and classification based on the gut microbiome might provide a promising approach to improve the prediction of patient outcome.</p>