Abstract
Background and aimRecent studies have proposed that commensal bacteria might be involved in the development and progression of gastrointestinal disorders such as colorectal cancer (CRC). Therefore, in this study, the relative abundance of Fusobacterium nucleatum, Bacteroides fragilis, Streptococcus bovis/gallolyticus, and Enteropathogenic Escherichia coli (EPEC) in CRC tissues, and their association with clinicopathologic characteristics of CRC was investigated in Iranian patients. Moreover, the role of these bacteria in the CRC-associated mutations including PIK3CA, KRAS, and BRAF was studied.MethodTo these ends, the noted bacteria were quantified in paired tumors and normal tissue specimens of 30 CRC patients, by TaqMan quantitative Real-Time Polymerase Chain Reaction (qPCR). Next, possible correlations between clinicopathologic factors and mutations in PIK3CA, KRAS, and BRAF genes were analyzed.ResultsIn studied samples, B. fragilis was the most abundant bacteria that was detected in 66 and 60% of paired tumor and normal samples, respectively. Furthermore, 15% of the B. fragilis-positive patients were infected with Enterotoxigenic B. fragilis (ETBF) in both adenocarcinoma and matched adjacent normal samples. F. nucleatum was also identified in 23% of tumors and 13% of adjacent normal tissue samples. Moreover, the relative abundance of these bacteria determined by 2-ΔCT was significantly higher in CRC samples than in adjacent normal mucosa (p < 0.05). On the other hand, our findings indicated that S. gallolyticus and EPEC, compared to adjacent normal mucosa, were not prevalent in CRC tissues. Finally, our results revealed a correlation between F. nucleatum-positive patients and the KRAS mutation (p = 0.02), while analyses did not show any association between bacteria and mutation in PIK3CA and BRAF genes.ConclusionThe present study is the first report on the analysis of different bacteria in CRC tissue samples of Iranian patients. Our findings revealed that F. nucleatum and B. fragilis might be linked to CRC. However, any link between gut microbiome dysbiosis and CRC remains unknown.
Highlights
Colorectal cancer (CRC) is identified as one of the leading causes of morbidity and mortality around the world
Our findings indicated that S. gallolyticus and Enteropathogenic Escherichia coli (EPEC), compared to adjacent normal mucosa, were not prevalent in colorectal cancer (CRC) tissues
Our results revealed a correlation between F. nucleatum-positive patients and the KRAS mutation (p = 0.02), while analyses did not show any association between bacteria and mutation in PIK3CA and BRAF genes
Summary
Colorectal cancer (CRC) is identified as one of the leading causes of morbidity and mortality around the world It is known as the third most prevalent cancer in Iran and its mortality rate has been growing in recent years [1,2,3]. The World Health Organization (WHO) reported in 2014 that the CRC incidence rate, among men, had been rapidly increased in the past decades in Eastern Europe and Asia, including Iran [6]. Hereditary forms, such as familial adenomatous polyposis and hereditary non-polyposis colon cancers, constitute less than 5% of CRCs, while the majority are sporadic cases caused by factors such as environmental exposures and lifestyle. The role of these bacteria in the CRC-associated mutations including PIK3CA, KRAS, and BRAF was studied
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