Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
Department of Gastroenterological Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan.
Clin Cancer Res. 2016 Nov 15;22(22):5574-5581. doi: 10.1158/1078-0432.CCR-16-1786. Epub 2016 Oct 21.
Fusobacterium nucleatum (F. nucleatum) is a component of the human microbiome that primarily inhabits the oral cavity. It causes periodontal disease and has also been implicated in the development of human cancers. Although there are several reports of the relationship between F. nucleatum and the clinical outcome in human cancers, its prognostic significance in esophageal cancer remains unclear.
We quantified F. nucleatum DNA in 325 resected esophageal cancer specimens by qPCR. Significant pathways in F. nucleatum-positive esophageal cancer tissues were identified by Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis using microarray data.
Esophageal cancer tissues contained significantly more F. nucleatum DNA than matched normal esophageal mucosa (P = 0.021; n = 60). F. nucleatum DNA was detected in 74 of 325 cases (23%). F. nucleatum DNA positivity was significantly associated with tumor stage, but not with sex, age, performance status, tobacco use, alcohol use, histology, tumor location, or preoperative treatment. F. nucleatum DNA positivity was also significantly associated with cancer-specific survival [log-rank P = 0.0039; univariate HR = 2.01; 95% confidence interval (CI), 1.22-3.23; P = 0.0068; multivariate HR = 1.78; 95% CI, 1.06-2.94; P = 0.031]. The top-ranked KEGG pathway in F. nucleatum-positive tissues was "cytokine-cytokine receptor interaction." A significant relationship between F. nucleatum and the chemokine CCL20 was validated by IHC.
F. nucleatum in esophageal cancer tissues was associated with shorter survival, suggesting a potential role as a prognostic biomarker. F. nucleatum might also contribute to aggressive tumor behavior through activation of chemokines, such as CCL20. Clin Cancer Res; 22(22); 5574-81. ©2016 AACR.
具核梭杆菌（F. nucleatum）是人类微生物组的一个组成部分，主要栖息在口腔中。它会引起牙周病，并且与人类癌症的发展也有关联。尽管有几项关于 F. nucleatum 与人类癌症临床结果之间关系的报告，但它在食管癌中的预后意义仍不清楚。
我们通过 qPCR 对 325 例切除的食管癌标本中的 F. nucleatum DNA 进行了定量。通过使用微阵列数据对 KEGG 富集分析，鉴定了 F. nucleatum 阳性食管癌组织中的显著通路。
食管癌组织中 F. nucleatum DNA 的含量明显高于匹配的正常食管黏膜（P = 0.021；n = 60）。在 325 例病例中，有 74 例（23%）检测到 F. nucleatum DNA。F. nucleatum DNA 阳性与肿瘤分期显著相关，但与性别、年龄、表现状态、吸烟、饮酒、组织学、肿瘤位置或术前治疗无关。F. nucleatum DNA 阳性也与癌症特异性生存显著相关[对数秩 P = 0.0039；单因素 HR = 2.01；95%置信区间（CI），1.22-3.23；P = 0.0068；多因素 HR = 1.78；95% CI，1.06-2.94；P = 0.031]。在 F. nucleatum 阳性组织中排名最高的 KEGG 通路是“细胞因子-细胞因子受体相互作用”。通过 IHC 验证了 F. nucleatum 与趋化因子 CCL20 之间的显著关系。
食管癌组织中的 F. nucleatum 与较短的生存时间相关，提示其可能作为预后生物标志物发挥作用。F. nucleatum 也可能通过激活趋化因子（如 CCL20）促进侵袭性肿瘤行为。临床癌症研究；22（22）；5574-81。©2016 AACR.
