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伴有或不伴有具核梭杆菌感染的胃癌的临床病理参数、预后、微生态环境及代谢功能比较

Comparison of clinicopathological parameters, prognosis, micro-ecological environment and metabolic function of Gastric Cancer with or without Fusobacterium sp. Infection.

作者信息

Nie Siru, Wang Ang, Yuan Yuan

机构信息

Tumor Etiology and Screening Department of Cancer Institute and General Surgery, The First Hospital of China Medical University, Shenyang 110001, China.

Key Laboratory of Cancer Etiology and Prevention in Liaoning Education Department, The First Hospital of China Medical University, Shenyang 110001, China.

出版信息

J Cancer. 2021 Jan 1;12(4):1023-1032. doi: 10.7150/jca.50918. eCollection 2021.

Abstract

Fusobacterium sp. plays a crucial role in the tumorigenesis and development of gastrointestinal tumors. Our research group previously disclosed that Fusobacterium sp. was more abundant in gastric cancer (GC) tissues than adjacent non-cancerous (NC) tissues. However, Fusobacterium sp. did not exist in all GC tissues and the differentiated features of GC with or without Fusobacterium sp. infection is not clear. The expression data of 61 GC tissues came from 16S rRNA gene sequencing. Comparison groups were defined based on sOTU at the genus level of Fusobacterium sp., which was performed by the Qiime2 microbiome bioinformatics platform. We used Chi-square and Fisher's exact test to compare clinicopathological parameters, and used Kaplan-Meier analysis, Cox univariate and multivariate analysis to compare prognosis. Micro-ecological environment comparison was characterized by 16S rRNA gene sequencing, and the metabolic function prediction was applied by PICRUSt2. Results of microbial diversity, differential enrichment genus and metabolic function in GC with or without Fusobacterium sp. infection was validated with 229 GC tissues downloaded from an independent cohort in ENA database (PRJNA428883). The infection rate of Fusobacterium sp. in 61 GC tissues was 52.46% and elderly GC patients were more prone to Fusobacterium sp. infection. GC patients infected with Fusobacterium sp. were more likely to have tumor-infiltrating lymphocytes and p53 expression. The microbial diversity and microbial structure showed significant differences between two GC tissue groups with 42 differential enrichment genera. The metabolic function of Fusobacterium sp.-positive GC tissues was related to the biosynthesis of lysine, peptidoglycan, and tRNA. The differences in microbial structure, the existence of some differential enrichment genera and the metabolic function of Fusobacterium sp.-positive GC tissues, were then validated by 229 GC tissues of an independent cohort. Fusobacterium sp. infection can affect the phenotypic characteristics, micro-ecological environment, and metabolic functions of GC, which may provide a basis for further exploring the relationship between Fusobacterium sp. infection and carcinogenesis of GC.

摘要

梭杆菌属在胃肠道肿瘤的发生和发展中起着关键作用。我们的研究小组之前发现,梭杆菌属在胃癌(GC)组织中比相邻的非癌(NC)组织中更为丰富。然而,并非所有GC组织中都存在梭杆菌属,且感染或未感染梭杆菌属的GC的分化特征尚不清楚。61例GC组织的表达数据来自16S rRNA基因测序。比较组是根据梭杆菌属属水平的sOTU定义的,这是通过Qiime2微生物组生物信息学平台进行的。我们使用卡方检验和Fisher精确检验来比较临床病理参数,并使用Kaplan-Meier分析、Cox单因素和多因素分析来比较预后。通过16S rRNA基因测序对微生态环境进行比较,并应用PICRUSt2进行代谢功能预测。从ENA数据库(PRJNA428883)的一个独立队列中下载的229例GC组织验证了感染或未感染梭杆菌属的GC中微生物多样性、差异富集属和代谢功能的结果。61例GC组织中梭杆菌属的感染率为52.46%,老年GC患者更容易感染梭杆菌属。感染梭杆菌属的GC患者更有可能出现肿瘤浸润淋巴细胞和p53表达。两个GC组织组之间的微生物多样性和微生物结构存在显著差异,有42个差异富集属。梭杆菌属阳性GC组织的代谢功能与赖氨酸、肽聚糖和tRNA的生物合成有关。然后,通过一个独立队列的229例GC组织验证了微生物结构的差异、一些差异富集属的存在以及梭杆菌属阳性GC组织的代谢功能。梭杆菌属感染可影响GC的表型特征、微生态环境和代谢功能,这可能为进一步探索梭杆菌属感染与GC致癌作用之间的关系提供依据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27dc/7797643/4e9eafaa4ca6/jcav12p1023g001.jpg

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