Fusobacterium nucleatum in colorectal carcinoma tissue and patient prognosis.
Fusobacterium nucleatum in colorectal carcinoma tissue and patient prognosis.
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DOI：
10.1136/gutjnl-2015-310101
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发表时间：
2016-12
期刊：
影响因子：
24.5
通讯作者：
Ogino S
中科院分区：
文献类型：
--
作者：
Mima K;Nishihara R;Qian ZR;Cao Y;Sukawa Y;Nowak JA;Yang J;Dou R;Masugi Y;Song M;Kostic AD;Giannakis M;Bullman S;Milner DA;Baba H;Giovannucci EL;Garraway LA;Freeman GJ;Dranoff G;Garrett WS;Huttenhower C;Meyerson M;Meyerhardt JA;Chan AT;Fuchs CS;Ogino S
越来越多的证据将肠道微生物区系与结直肠癌的发生联系起来。核梭杆菌可促进结直肠癌生长，抑制T细胞介导的抗结直肠癌免疫反应。因此，我们假设结直肠癌中核梭杆菌的数量可能与较差的临床结果有关。我们利用护士健康研究和卫生专业人员随访研究中1069例直肠癌和结肠癌患者的分子病理流行病学数据库，检测了癌组织中的核梭杆菌DNA。用Cox比例风险模型计算危险比(HR)，控制潜在的混杂因素，包括微卫星不稳定性(MSI，错配修复缺陷)、CpG岛甲基化表型(CIMP)、KRAS、BRAF和PIK3CA突变，以及Line-1低甲基化(低甲基化)。与阴性病例相比，低核梭杆菌病例和高核梭杆菌病例对结直肠癌特异性死亡率的多变量RR(95%可信区间)分别为1.25(0.82~1.92)和1.58(1.04~2.39)(趋势P=0.020)。核梭杆菌的数量与MSI高相关(多变量优势比，5.22；95%可信区间，2.86~9.55)独立于CIMP和BRAF突变状态，而CIMP和BRAF突变仅在单变量分析中与核梭杆菌相关(p<；0.001)，但在调整MSI状态的多变量分析中不相关。结直肠癌组织中核梭杆菌DNA的数量与较短的生存期有关，并可能成为预测预后的生物标志物。我们的数据可能对通过饮食、益生菌和抗生素靶向胃肠道微生物群来制定癌症预防和治疗策略具有指导意义。
Accumulating evidence links the intestinal microbiota and colorectal carcinogenesis. Fusobacterium nucleatum may promote colorectal tumour growth and inhibit T-cell-mediated immune responses against colorectal tumours. Thus, we hypothesized that the amount of Fusobacterium nucleatum in colorectal carcinoma might be associated with worse clinical outcome. We utilised molecular pathological epidemiology database of 1,069 rectal and colon cancer cases in the Nurses’ Health Study and the Health Professionals Follow-up Study, and measured Fusobacterium nucleatum DNA in carcinoma tissue. Cox proportional hazards model was used to compute hazard ratio (HR), controlling for potential confounders, including microsatellite instability (MSI, mismatch repair deficiency), CpG island methylator phenotype (CIMP), KRAS, BRAF, and PIK3CA mutations, and LINE-1 hypomethylation (low-level methylation). Compared to Fusobacterium nucleatum-negative cases, multivariable HRs (95% confidence interval) for colorectal cancer-specific mortality in Fusobacterium nucleatum-low cases and Fusobacterium nucleatum-high cases were 1.25 (0.82 to 1.92) and 1.58 (1.04 to 2.39), respectively (p for trend = 0.020). The amount of Fusobacterium nucleatum was associated with MSI-high (multivariable odds ratio, 5.22; 95% CI, 2.86 to 9.55) independent of CIMP and BRAF mutation status, whereas CIMP and BRAF mutation were associated with Fusobacterium nucleatum only in univariate analyses (p < 0.001) but not in multivariate analysis that adjusted for MSI status. The amount of Fusobacterium nucleatum DNA in colorectal cancer tissue is associated with shorter survival, and may potentially serve as a prognostic biomarker. Our data may have implications in developing cancer prevention and treatment strategies through targeting gastrointestinal microflora by diet, probiotics, and antibiotics.