Evaluation of enterotoxigenic Bacteroides fragilis correlation with the expression of cellular signaling pathway genes in Iranian patients with colorectal cancer

Abstract

Background Colorectal cancer (CRC) is one of the most common cancers all over the world, and dysbiosis in the gut microbiota may play a role in colorectal carcinogenesis. Bacteroides fragilis can lead to tumorigenesis by changing signaling pathways, including the WNT/β-catenin pathway. Therefore, in the present study, we investigated the correlation between the enterotoxigenic B. fragilis amount and the expression of signaling pathway genes involved in CRC. Materials and methods B. fragilis was determined in 30 tumors and adjacent healthy tissues by the qPCR method. Next, the relationship between enterotoxigenic B. fragilis and the expression of signaling pathway genes, including CCND1, TP53, BCL2, BAX, WNT, TCF, AXIN, APC, and CTNNB1 was investigated. Additionally, possible correlations between clinicopathological features of the tumor samples and the abundance of B. fragilis were analyzed. Results The results showed that B. fragilis was detected in 100% of tumor samples and 86% of healthy tissues. Additionally, enterotoxigenic B. fragilis colonized 47% of all samples, and bft-1 toxin was the most frequently found isotype among the samples. The analysis showed that the high level of B. fragilis has a significant relationship with the high expression of AXIN, CTNNB1, and BCL2 genes. On the other hand, our results did not show any possible correlation between this bacterium and the clinicopathological features of the tumor sample. Conclusion B. fragilis had a higher abundance in the tumor samples than in healthy tissues, and this bacterium may lead to CRC by making changes in cellular signaling pathways and genes. Therefore, to better understand the physiological effects of B. fragilis on the inflammatory response and CRC, future research should focus on dissecting the molecular mechanisms by which this bacterium regulates cellular signaling pathways.

Immune landscape in APC and TP53 related tumor microenvironment in colon adenocarcinoma: A bioinformatic analysis

“…The differential expression analysis demonstrated significantly higher levels of APC and TP53 mRNA in tumor samples compared to normal colon tissue [ 24–26 ]. This upregulation of APC and TP53 in COAD is consistent with their known roles as oncogenes in COAD.…”

Microbiome Dysbiosis, Dietary Intake and Lifestyle-Associated Factors Involve in Epigenetic Modulations in Colorectal Cancer: A Narrative Review

“… 55 By stimulating the Wnt/B-catenin pathway through its BFT activities, enterotoxigenic B. Fragilis promotes cell proliferation and growth in the pathophysiology of colorectal cancer. 56 The toxin also enhances the release of inflammatory molecules from the epithelial cells, which triggers carcinogenesis by activating the NF-κB signaling pathway. 56 Also, ETBF has been reported to specifically stimulate signal transducer and activator of transcription-3 (STATA3) in the colon, causing Th17 infiltration and advancement of colorectal cancer.…”

“… 56 The toxin also enhances the release of inflammatory molecules from the epithelial cells, which triggers carcinogenesis by activating the NF-κB signaling pathway. 56 Also, ETBF has been reported to specifically stimulate signal transducer and activator of transcription-3 (STATA3) in the colon, causing Th17 infiltration and advancement of colorectal cancer. 57 Furthermore, the colonic epithelia cells that attach ETBF to them are stimulated to cleave the tumor-suppressor E-cadherin, which increases the permeability of the cells.…”