目的:最近的研究表明共生菌可能参与了胃肠道疾病如结直肠癌(CRC)的发生和发展。因此,在这项研究中,具核梭杆菌的相对丰度,脆弱拟杆菌,牛链球菌/溶胆囊,和CRC组织中的肠致病性大肠杆菌(EPEC),在伊朗患者中研究了它们与CRC临床病理特征的关系.此外,这些细菌在CRC相关突变中的作用,包括PIK3CA,KRAS,并对BRAF进行了研究。
方法:为此,对30例CRC患者的配对肿瘤和正常组织标本中的细菌进行定量,通过TaqMan定量实时聚合酶链反应(qPCR)。接下来,临床病理因素与PIK3CA突变之间的可能相关性,KRAS,并对BRAF基因进行了分析。
结果:在研究的样本中,脆弱芽孢杆菌是在66%和60%的配对肿瘤和正常样品中检测到的最丰富的细菌,分别。此外,在腺癌和匹配的邻近正常样本中,15%的脆弱芽孢杆菌阳性患者感染肠毒素脆弱芽孢杆菌(ETBF)。在23%的肿瘤和13%的邻近正常组织样品中也鉴定出核F.此外,通过2-ΔCT确定的这些细菌的相对丰度在CRC样品中明显高于邻近的正常粘膜(p<0.05)。另一方面,我们的研究结果表明,胆溶菌和EPEC,与邻近的正常粘膜相比,在CRC组织中并不普遍。最后,我们的结果揭示了F.Nucleum阳性患者与KRAS突变之间的相关性(p=0.02),而分析未显示细菌与PIK3CA和BRAF基因突变之间有任何关联.
结论:本研究是关于伊朗患者CRC组织样本中不同细菌分析的第一份报告。我们的发现表明,核仁F.和脆弱芽孢杆菌可能与CRC有关。然而,肠道微生物群失调和CRC之间的任何联系仍然未知.
OBJECTIVE: Recent 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.
METHODS: To 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.
RESULTS: In 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.
CONCLUSIONS: The 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.