Fusobacterium nucleatum as a prognostic marker of colorectal cancer in a Japanese population

Fusobacterium nucleatum as a prognostic marker of colorectal cancer in a Japanese population
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DOI:
10.1007/s00535-017-1382-6
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发表时间:
2018-04-01
影响因子:
6.3
通讯作者:
Yamasaki, Takahiro
Yamasaki, Takahiro
中科院分区:
医学1区
文献类型:
--
作者:
Yamaoka, Yuko;Suehiro, Yutaka;Yamasaki, Takahiro

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越来越多的证据表明,结肠肿瘤组织中存在大量的核梭杆菌。然而,从以往的报道来看,结直肠癌组织中核颤菌的绝对拷贝数与结直肠癌进展之间的相关性尚不清楚。因此,我们收集了100例结直肠癌组织和72例匹配的正常粘膜组织,比较了结直肠癌组织中核杆菌的丰度与结直肠癌的临床病理和分子特征的关系。液滴数字聚合酶链式反应检测核纤毛虫的绝对拷贝数,在正常粘膜组织中的阳性率为63.9%(46/72),在结直肠癌组织中的阳性率为75.0%(75/100)。结直肠癌患者正常大肠黏膜组织中核纤丝酵母菌的拷贝数中位数为0.4ngDNA,而结直肠癌组织中的中位拷贝数为1.9ngDNA(P=0.0031)。IV期结直肠癌组织中F.核型拷贝数显著高于正常组织(P=0.0016)。结直肠癌组织中核革兰氏杆菌的丰度与肿瘤大小和KRAS突变相关,与总生存期缩短显著相关;这一趋势在IV期结直肠癌患者中尤为明显。针对结直肠癌患者外观正常的粘膜,核纤毛虫拷贝数在IV期患者明显高于I-III期患者。这一结果提示,测定核纤毛虫水平有助于预测结直肠癌患者的临床预后。需要使用独立数据集进行进一步的验证性研究来证实我们的发现。
Accumulating evidence shows an overabundance of Fusobacterium nucleatum in colorectal tumor tissues. However, the correlation between the absolute copy number of F. nucleatum in colorectal cancer tissues and colorectal cancer progression is unclear from previous reports. Therefore, we performed a study to compare the abundance of F. nucleatum in colorectal tissues with clinicopathologic and molecular features of colorectal cancer.We collected 100 colorectal cancer tissues and 72 matched normal-appearing mucosal tissues. Absolute copy numbers of F. nucleatum were measured by droplet digital PCR.The detection rates of F. nucleatum were 63.9% (46/72) in normal-appearing mucosal tissues and 75.0% (75/100) in CRC tissue samples. The median copy number of F. nucleatum was 0.4/ng DNA in the normal-appearing colorectal mucosa in patients with colorectal cancer and 1.9/ng DNA in the colorectal cancer tissues (P = 0.0031). F. nucleatum copy numbers in stage IV colorectal cancer tissues were significantly higher than those in the normal-appearing mucosa in patients with colorectal cancer (P = 0.0016). The abundance of F. nucleatum in colorectal cancer tissues correlated with tumor size and KRAS mutation and was significantly associated with shorter overall survival times; this trend was notable in the patients with stage IV colorectal cancer. Focusing on normal-appearing mucosa in the patients with colorectal cancer, the F. nucleatum copy number was significantly higher in the patients with stage IV rather than stages I-III.These results suggest that determining F. nucleatum levels may help predict clinical outcomes in colorectal cancer patients. Further confirmatory studies using independent datasets are required to confirm our findings.