Novel Discoveries Targeting Pathogenic Gut Microbes and New Therapies in Pancreatic Cancer: Does Pathogenic E. coli Infection Cause Pancreatic Cancer Progression Modulated by TUBB/Rho/ROCK Signaling Pathway? A Bioinformatic Analysis
Novel Discoveries Targeting Pathogenic Gut Microbes and New Therapies in Pancreatic Cancer: Does Pathogenic E. coli Infection Cause Pancreatic Cancer Progression Modulated by TUBB/Rho/ROCK Signaling Pathway? A Bioinformatic Analysis
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DOI：
10.1155/2020/2340124
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发表时间：
2020-05-11
影响因子：
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通讯作者：
Zhang, Taiping
中科院分区：
文献类型：
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作者：
Luo, Wenhao;Cao, Zhe;Zhang, Taiping
胰腺癌（PC）是一种恶性程度较高的消化系统恶性肿瘤。越来越多的研究表明，调节肠道微生物组可能成为改善PC治疗效果的一种全新策略。本研究的目的是获得PC的微生物致瘤途径。微阵列数据集GSE 27890、GSE 46234和GSE 17610从GEO（Gene Expression Omnibus）数据库下载。使用R软件包（“Limma”包）对每个单基因芯片进行差异分析，并通过大卫（用于注释、可视化和集成发现的数据库）进行功能富集分析。PPI（蛋白质-蛋白质相互作用）网络的构建与检索工具的相互作用基因（STRING）。生存分析由GEPIA和USCS进行。共鉴定了84个差异表达基因（DEG），并提取了其中的3个（TUBB、TUBA 4A和TLR 5）。生物学过程分析表明，这3个基因主要在致病性大肠杆菌（E. coli）感染。生存分析和通路分析显示TUBB（tubulin，beta class I）可能与致病性E.大肠杆菌感染，可能通过激活TUBB/Rho/ROCK信号通路参与PC的发生、发展。有证据表明，特定的肠道微生物可以通过抑制免疫反应来影响PC的进展。然而，很少有人关注TUBB/Rho/ROCK信号转导，微生物和PC之间的关系和串扰。本文旨在推断肠道和肿瘤微生物通过刺激TUBB/Rho/ROCK信号通路与PC的发生发展相关，而抗生素与TUBB/Rho/ROCK信号通路抑制剂联合治疗微生物被确定为PC治疗的新靶点。
Pancreatic cancer (PC) is a pernicious cancer of the digestive system which remains a high degree of malignancy. Increasing studies demonstrated that regulating the gut microbiome may become a brand new strategy to improve the therapeutic outcomes of PC. This study is aimed at obtaining the pathway in the microbial tumorigenesis of PC. Microarray datasets GSE27890, GSE46234, and GSE17610 were downloaded from the GEO (Gene Expression Omnibus) database. Differential analysis was performed for every single gene chip using the R software package ("Limma" package), and functional enrichment analyses were carried out by DAVID (Database for Annotation, Visualization and Integrated Discovery). The PPI (protein-protein interaction) network was constructed with the Search Tool for the Retrieval of Interacting Genes (STRING). The survival analysis was performed by GEPIA and USCS. A total of 84 differentially expressed genes (DEGs) were identified, and 3 of them were extracted (TUBB, TUBA4A, and TLR5). Biological process analysis revealed that these 3 genes were mainly enriched in pathogenic Escherichia coli (E. coli) infection. Survival analysis and pathway analysis revealed that TUBB (tubulin, beta class I) may be associated with the pathogenic E. coli infection, which may be involved in the carcinogenesis and progression of PC by activating the TUBB/Rho/ROCK signaling pathway. Elevated evidence indicated that a specific gut microbe could affect the progression of PC by suppressing immune response. However, little attention has been paid to the relationship and crosstalk between TUBB/Rho/ROCK signaling, microbes, and PC. This article is aimed at deducing that gut and tumor microbes are related to the development of PC by stimulating TUBB/Rho/ROCK signaling, while ablation of microbes by antibiotics cotreated with inhibitors of TUBB/Rho/ROCK signaling were identified as a novel target for PC therapy.