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解析组织定植微生物组在卵巢癌进展中的作用。

Unraveling the role of tissue colonized microbiome in ovarian cancer progression.

机构信息

The Department of Obstetrics and Gynecology, The First Affiliated Hospital of Harbin Medical University, Harbin Medical University, Harbin, 150007, Heilongjiang, China.

College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, Heilongjiang, China.

出版信息

Comput Biol Med. 2024 Jul;177:108641. doi: 10.1016/j.compbiomed.2024.108641. Epub 2024 May 24.

DOI:10.1016/j.compbiomed.2024.108641
PMID:38833797
Abstract

BACKGROUND

Ovarian cancer (OC) is found to be the third most common gynecologic malignancy over the world, having the highest mortality rate among such tumors. Emerging studies underscore the presence of microorganisms within tumor tissues, with certain pathogens intricately linked to disease onset and progression. Disruption of the microbiome frequently precipitates disturbances in host metabolic and immune pathways, thereby fostering the development of cancer.

METHODS

In this study, we initiated the investigation by conducting microbial reannotation on the RNA sequencing data derived from ovarian cancer tissues. Subsequently, a comprehensive array of analyses on tissue microbes was executed. These analyses encompassed the assessment of intergroup variations in microbial diversity, differential microbiological analysis, exploration of the association between host gene expression and microbial abundance, as well as an enrichment analysis of functional pathways linked to host genes associated with microbes.

RESULTS

The analysis results revealed that Proteobacteria, Actinobacteria, Firmicutes, and Bacteroidetes were the main components at phylum level in ovarian tissue. Notably, the microbial composition of ovarian cancer tissue significantly diverged from that of normal ovarian tissue e, exhibiting markedly lower alpha diversity and distinct beta diversity. Besides, pathogenic microorganisms Achromobacter xylosoxidans and Enterobacter hormaechei were enriched in cancer tissue. Host genes associated with these pathogens were enriched in key pathways including "JAK-STAT signaling pathway", "Transcriptional misregulation in cancer", and "Th1 and Th2 cell differentiation", suggesting their role in ovarian cancer progression through microbial dysbiosis and immune response interaction.

CONCLUSION

Abundance of pathogenic microorganisms in ovarian cancer tissue could modulate the expression of host genes, consequently impacting cancer-related signaling pathways and fostering cancer progression.

摘要

背景

卵巢癌(OC)是全球第三大常见妇科恶性肿瘤,其肿瘤死亡率最高。新兴研究强调肿瘤组织内存在微生物,某些病原体与疾病的发生和进展密切相关。微生物组的破坏常常导致宿主代谢和免疫途径紊乱,从而促进癌症的发展。

方法

在这项研究中,我们首先对卵巢癌组织的 RNA 测序数据进行微生物重新注释,然后对组织微生物进行了全面的分析。这些分析包括评估微生物多样性的组间差异、差异微生物分析、宿主基因表达与微生物丰度之间的关联探索,以及与宿主基因相关的微生物功能途径的富集分析。

结果

分析结果表明,厚壁菌门、放线菌门、Firmicutes 和 Bacteroidetes 是卵巢组织中主要的门水平组成部分。值得注意的是,卵巢癌组织的微生物组成与正常卵巢组织显著不同,表现出明显较低的 alpha 多样性和明显不同的 beta 多样性。此外,致病性微生物 Achromobacter xylosoxidans 和 Enterobacter hormaechei 在癌症组织中富集。与这些病原体相关的宿主基因在关键途径中富集,包括“JAK-STAT 信号通路”、“癌症中的转录失调”和“Th1 和 Th2 细胞分化”,表明它们通过微生物失调和免疫反应相互作用在卵巢癌进展中发挥作用。

结论

卵巢癌组织中致病性微生物的丰度可能调节宿主基因的表达,从而影响与癌症相关的信号通路并促进癌症进展。

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