BC Cancer Agency, Michael Smith Genome Sciences Centre, Vancouver, British Columbia V5Z 1L3, Canada.
Genome Res. 2012 Feb;22(2):299-306. doi: 10.1101/gr.126516.111. Epub 2011 Oct 18.
An estimated 15% or more of the cancer burden worldwide is attributable to known infectious agents. We screened colorectal carcinoma and matched normal tissue specimens using RNA-seq followed by host sequence subtraction and found marked over-representation of Fusobacterium nucleatum sequences in tumors relative to control specimens. F. nucleatum is an invasive anaerobe that has been linked previously to periodontitis and appendicitis, but not to cancer. Fusobacteria are rare constituents of the fecal microbiota, but have been cultured previously from biopsies of inflamed gut mucosa. We obtained a Fusobacterium isolate from a frozen tumor specimen; this showed highest sequence similarity to a known gut mucosa isolate and was confirmed to be invasive. We verified overabundance of Fusobacterium sequences in tumor versus matched normal control tissue by quantitative PCR analysis from a total of 99 subjects (p = 2.5 × 10(-6)), and we observed a positive association with lymph node metastasis.
据估计,全球约 15%或更多的癌症负担可归因于已知的感染因子。我们使用 RNA-seq 对结直肠癌和匹配的正常组织标本进行了筛选,然后通过宿主序列减法发现,与对照标本相比,肿瘤中 Fusobacterium nucleatum 序列的过度表达明显。Fusobacterium nucleatum 是一种侵袭性厌氧菌,先前与牙周炎和阑尾炎有关,但与癌症无关。梭菌是粪便微生物群中罕见的组成部分,但以前已从发炎的肠道黏膜活检中培养出来。我们从冷冻的肿瘤标本中获得了一种梭菌分离物;该分离物与已知的肠道黏膜分离物具有最高的序列相似性,并且被证实具有侵袭性。我们通过对 99 名患者(p = 2.5 × 10(-6))的总定量 PCR 分析,验证了肿瘤与匹配的正常对照组织中 Fusobacterium 序列的过度表达,并观察到与淋巴结转移呈正相关。