Mitsuhashi Kei, Nosho Katsuhiko, Sukawa Yasutaka, Matsunaga Yasutaka, Ito Miki, Kurihara Hiroyoshi, Kanno Shinichi, Igarashi Hisayoshi, Naito Takafumi, Adachi Yasushi, Tachibana Mami, Tanuma Tokuma, Maguchi Hiroyuki, Shinohara Toshiya, Hasegawa Tadashi, Imamura Masafumi, Kimura Yasutoshi, Hirata Koichi, Maruyama Reo, Suzuki Hiromu, Imai Kohzoh, Yamamoto Hiroyuki, Shinomura Yasuhisa
Department of Gastroenterology, Rheumatology and Clinical Immunology, Sapporo Medical University School of Medicine, Sapporo, Japan.
Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.
Oncotarget. 2015 Mar 30;6(9):7209-20. doi: 10.18632/oncotarget.3109.
Recently, bacterial infection causing periodontal disease has attracted considerable attention as a risk factor for pancreatic cancer. Fusobacterium species is an oral bacterial group of the human microbiome. Some evidence suggests that Fusobacterium species promote colorectal cancer development; however, no previous studies have reported the association between Fusobacterium species and pancreatic cancer. Therefore, we examined whether Fusobacterium species exist in pancreatic cancer tissue. Using a database of 283 patients with pancreatic ductal adenocarcinoma (PDAC), we tested cancer tissue specimens for Fusobacterium species. We also tested the specimens for KRAS, NRAS, BRAF and PIK3CA mutations and measured microRNA-21 and microRNA-31. In addition, we assessed epigenetic alterations, including CpG island methylator phenotype (CIMP). Our data showed an 8.8% detection rate of Fusobacterium species in pancreatic cancers; however, tumor Fusobacterium status was not associated with any clinical and molecular features. In contrast, in multivariate Cox regression analysis, compared with the Fusobacterium species-negative group, we observed significantly higher cancer-specific mortality rates in the positive group (p = 0.023). In conclusion, Fusobacterium species were detected in pancreatic cancer tissue. Tumor Fusobacterium species status is independently associated with a worse prognosis of pancreatic cancer, suggesting that Fusobacterium species may be a prognostic biomarker of pancreatic cancer.
最近，作为胰腺癌的一个风险因素，导致牙周病的细菌感染已引起了相当多的关注。梭杆菌属是人类微生物群中的一个口腔细菌群。一些证据表明梭杆菌属促进结直肠癌的发展；然而，以前没有研究报道过梭杆菌属与胰腺癌之间的关联。因此，我们检测了胰腺癌组织中是否存在梭杆菌属。利用一个包含283例胰腺导管腺癌（PDAC）患者的数据库，我们对癌组织标本进行了梭杆菌属检测。我们还对标本进行了KRAS、NRAS、BRAF和PIK3CA突变检测，并测量了微小RNA-21和微小RNA-31。此外，我们评估了表观遗传改变，包括CpG岛甲基化表型（CIMP）。我们的数据显示胰腺癌中梭杆菌属的检出率为8.8%；然而，肿瘤梭杆菌属状态与任何临床和分子特征均无关联。相比之下，在多变量Cox回归分析中，与梭杆菌属阴性组相比，我们观察到阳性组的癌症特异性死亡率显著更高（p = 0.023）。总之，在胰腺癌组织中检测到了梭杆菌属。肿瘤梭杆菌属状态与胰腺癌的预后较差独立相关，这表明梭杆菌属可能是胰腺癌的一个预后生物标志物。
