Novel Discoveries Targeting Pathogenic Gut Microbes and New Therapies in Pancreatic Cancer: Does Pathogenic E. coli Infection Cause Pancreatic Cancer Progression Modulated by TUBBRhoROCK Signaling Pathway? A Bioinformatic Analysis

Abstract EN

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.