Abstract 4930: Genetic and epigenetic characteristics of esophageal cancer tissues with microbiome fusobacterium nucleatum

Abstract

Abstract Background: Research into the microbiome is a rapidly advancing field in human cancers. The gut microbiome has recently been shown to play an important role in health, as well as in diseases such as obesity, inflammatory bowel disease, diabetes, non-alcoholic fatty liver disease, and several types of cancers. Fusobacterium 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. We have recently reported that Fusobacterium nucleatum in esophageal cancer tissues was associated with shorter survival, suggesting a potential role as a prognostic biomarker. In addition, our KEGG enrichment analysis using microarray data showed that Fusobacterium nucleatum might also contribute to aggressive tumor behavior through activation of chemokines such as CCL20. Nonetheless, molecular features of Fusobacterium nucleatum-positive esophageal cancers have been still unknown. Methods: Using 325 esophageal cancers, we detected Fusobacterium nucleatum DNA in 74 tumors (23%). We assessed other genetic and epigenetic events including mutations in KRAS, BRAF, PIK3CA gene, p53 expression, phosphorylated-AKT expression, LINE-1 methylation level (global DNA methylation level), IGF2 DMR0 methylation, MGMT methylation, and MLH1 methylation. Results: The LINE-1 methylation levels of Fusobacterium nucleatum-positive tumors was significantly lower compared with that of Fusobacterium nucleatum-negative tumors (P<0.0001). In addition, Fusobacterium nucleatum was significantly associated with PIK3CA wild type (P=0.010). There was no relationship of Fusobacterium nucleatum with KRAS, BRAF mutation, p53 expression, p-AKT expression, IGF2 DMR0 methylation, MGMT methylation, or MLH1 methylation. Conclusion: Fusobacterium nucleatum was related with LINE-1 hypomethylation and PIK3CA wild type. Our findings may shed lights on understanding the mechanism by which Fusobacterium nucleatum affects aggressive tumor behavior. . Citation Format: Yoshifumi Baba, Kensuke Yamamura, Shigeki Nakagawa, Kosuke Mima, Takatsugu Ishimoto, Masaaki Iwatsuki, Yasuo Sakamoto, Naoya Yoshida, Hideo Baba. Genetic and epigenetic characteristics of esophageal cancer tissues with microbiome fusobacterium nucleatum [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4930. doi:10.1158/1538-7445.AM2017-4930