Fusobacterium in colonic flora and molecular features of colorectal carcinoma.
Fusobacterium in colonic flora and molecular features of colorectal carcinoma.
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结肠菌群和大肠癌的分子特征中的梭杆菌。
DOI：
10.1158/0008-5472.can-13-1865
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发表时间：
2014-03-01
期刊：
影响因子：
11.2
通讯作者：
Issa JP
中科院分区：
文献类型：
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作者：
Tahara T;Yamamoto E;Suzuki H;Maruyama R;Chung W;Garriga J;Jelinek J;Yamano HO;Sugai T;An B;Shureiqi I;Toyota M;Kondo Y;Estécio MR;Issa JP
梭杆菌属是人类肠道微生物组的一部分。最近的研究已经确定了结直肠癌（CRC）组织中梭杆菌的过度表达，但尚不清楚这是致病性还是仅仅是一种附带现象。在这项研究中，我们通过定量实时PCR在149个CRC组织，89个相邻的正常粘膜和72个结肠粘膜的无癌个体中评估梭杆菌状态和CRC分子特征之间的关系。结果与CpG岛甲基化表型（CIMP）状态，微卫星不稳定性（MSI）和BRAF，KRAS，TP 53，CHD 7和CHD 8突变相关。在11个病例中也可获得全外显子组捕获测序数据。在111/149（74%）的CRC组织中可检测到梭杆菌，并在9%（14/149）的病例中高度富集。正如预期的那样，在癌症和无癌症个体的正常粘膜中也检测到梭杆菌，但细菌的量比CRC组织低得多（泛梭杆菌平均低250倍）。我们发现梭杆菌高CRC组（FB高）与CIMP阳性（p=0.001）、TP 53野生型（p=0.015）、hMLH 1甲基化阳性（p=0.0028）、MSI（p=0.018）和CHD 7/8突变阳性（p=0.002）相关。在11例全外显子组测序数据可用的病例中，两例FB高病例也具有最高数量的体细胞突变（FB高病例中每例平均736个，而所有其他病例中每例平均225个）。总之，我们的研究结果表明，梭杆菌富集与CRC的特定分子亚群相关，为这种肠道微生物组成分在CRC中的致病作用提供了支持
Fusobacterium species are part of the gut microbiome in humans. Recent studies have identified over-representation of Fusobacterium in colorectal cancer (CRC) tissues but it is not yet clear whether this is pathogenic or simply an epiphenomenon. In this study, we evaluated the relationship between Fusobacterium status and molecular features in CRCs through quantitative real-time PCR in 149 CRC tissues, 89 adjacent normal appearing mucosae and 72 colonic mucosae from cancer-free individuals. Results were correlated with CpG island methylator phenotype (CIMP) status, microsatellite instability (MSI) and mutations in BRAF, KRAS, TP53, CHD7 and CHD8. Whole exome capture sequencing data were also available in 11 cases. Fusobacterium was detectable in 111/149 (74%) CRC tissues and heavily enriched in 9% (14/149) of the cases. As expected, Fusobacterium was also detected in normal appearing mucosae from both cancer and cancer-free individuals but the amount of bacteria was much lower compared to CRC tissues (a mean of 250-fold lower for Pan-fusobacterium). We found the Fusobacterium-high CRC group (FB-high) to be associated with CIMP positivity (p=0.001), TP53 wild type (p=0.015), hMLH1 methylation positivity (p=0.0028), MSI (p=0.018) and CHD7/8 mutation positivity (p=0.002). Among the 11 cases where whole exome sequencing data was available, two that were FB-high cases also had the highest number of somatic mutations (a mean of 736 per case in FB-high vs. 225 per case in all others). Taken together, our findings show that Fusobacterium enrichment is associated with specific molecular subsets of CRCs, offering support for a pathogenic role in CRC for this gut microbiome component