4.6 Article

Fusobacterium Nucleatum-Induced Tumor Mutation Burden Predicts Poor Survival of Gastric Cancer Patients

期刊

CANCERS
卷 15, 期 1, 页码 -

出版社

MDPI
DOI: 10.3390/cancers15010269

关键词

Helicobacter pylori; Fusobacterium nucleatum; tumor mutation burden; gastric cancer

类别

向作者/读者索取更多资源

Gastric cancer is the fifth most common cancer in the world. The presence of pathogenic microbiota, such as Helicobacter pylori, is an important risk factor for the development of alimentary tract cancers. This study investigated the mutational landscape of F. nucleatum-positive gastric cancer tissues and identified genetic aberrations, including activating mutations of ERBB2, ERBB3, and PIK3CA, disrupted TP53, and high tumor mutational burden, all of which were associated with poor prognosis. These findings suggest that F. nucleatum infection and tumor mutational burden are strong biomarkers for the prognosis of gastric cancer.
Simple Summary Gastric cancer is the fifth most common cancer in the world. An important risk factor in the development of alimentary tract cancers is the presence of pathogenic microbiota, such as Helicobacter pylori. We previously showed that sporadic infection of Fusobacterium nucleatum is associated with disease progression. Therefore, we examined the mutational landscape of F. nucleatum-positive, resected gastric cancer tissues using the Illumina TruSight Oncology 500 comprehensive panel to identify small nucleotide variants, small insertions and deletions, and unstable microsatellite sites. We identified a number of recurrent genetic aberrations, especially activating mutations of ERBB2, ERBB3, and PIK3CA and disrupted TP53. We found that the combination of F. nucleatum infection and high tumor mutational burden was a strong predictor of poor prognosis. Thus, F. nucleatum infection is correlated with increased accumulation of mutations and progression of gastric cancer, and these factors may be useful in the prognosis of this disease. Co-infection of Helicobacter pylori and Fusobacterium nucleatum is a microbial biomarker for poor prognosis of gastric cancer patients. Fusobacterium nucleatum is associated with microsatellite instability and the accumulation of mutations in colorectal cancer. Here, we investigated the mutation landscape of Fusobacterium nucleatum-positive resected gastric cancer tissues using Illumina TruSight Oncology 500 comprehensive panel. Sequencing data were processed to identify the small nucleotide variants, small insertions and deletions, and unstable microsatellite sites. The bioinformatic algorithm also calculated copy number gains of preselected genes and tumor mutation burden. The recurrent genetic aberrations were identified in this study cohort. For gene amplification events, ERBB2, cell cycle regulators, and specific FGF ligands and receptors were the most frequently amplified genes. Pathogenic activation mutations of ERBB2, ERBB3, and PIK3CA, as well as loss-of-function of TP53, were identified in multiple patients. Furthermore, Fusobacterium nucleatum infection is positively correlated with a higher tumor mutation burden. Survival analysis showed that the combination of Fusobacterium nucleatum infection and high tumor mutation burden formed an extremely effective biomarker to predict poor prognosis. Our results indicated that the ERBB2-PIK3-AKT-mTOR pathway is frequently activated in gastric cancer and that Fusobacterium nucleatum and high mutation burden are strong biomarkers of poor prognosis for gastric cancer patients.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.6
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据