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伊朗结直肠癌患者中产肠毒素脆弱拟杆菌与细胞信号通路基因表达的相关性评估

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

作者信息

Dadgar-Zankbar Leila, Shariati Aref, Bostanghadiri Narjess, Elahi Zahra, Mirkalantari Shiva, Razavi Shabnam, Kamali Fatemeh, Darban-Sarokhalil Davood

机构信息

Department of Microbiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.

Molecular and Medicine Research Center, Khomein University of Medical Sciences, Khomein, Iran.

出版信息

Infect Agent Cancer. 2023 Aug 29;18(1):48. doi: 10.1186/s13027-023-00523-w.

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.

摘要

背景

结直肠癌(CRC)是全球最常见的癌症之一,肠道微生物群失调可能在结直肠癌发生过程中起作用。脆弱拟杆菌可通过改变信号通路(包括WNT/β-连环蛋白通路)导致肿瘤发生。因此,在本研究中,我们调查了产肠毒素脆弱拟杆菌数量与结直肠癌中涉及的信号通路基因表达之间的相关性。

材料与方法

采用qPCR法测定30例肿瘤组织及相邻健康组织中的脆弱拟杆菌。接下来,研究产肠毒素脆弱拟杆菌与信号通路基因(包括CCND1、TP53、BCL2、BAX、WNT、TCF、AXIN、APC和CTNNB1)表达之间的关系。此外,分析了肿瘤样本的临床病理特征与脆弱拟杆菌丰度之间的可能相关性。

结果

结果显示,100%的肿瘤样本和86%的健康组织中检测到脆弱拟杆菌。此外,产肠毒素脆弱拟杆菌定殖于所有样本的47%,bft-1毒素是样本中最常见的亚型。分析表明,脆弱拟杆菌的高水平与AXIN、CTNNB1和BCL2基因的高表达有显著关系。另一方面,我们的结果未显示该细菌与肿瘤样本的临床病理特征之间有任何可能的相关性。

结论

脆弱拟杆菌在肿瘤样本中的丰度高于健康组织,这种细菌可能通过改变细胞信号通路和基因导致结直肠癌。因此,为了更好地理解脆弱拟杆菌对炎症反应和结直肠癌的生理影响,未来的研究应集中于剖析该细菌调节细胞信号通路的分子机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff39/10463534/66c6ee010640/13027_2023_523_Fig1_HTML.jpg

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