肿瘤内微生物群的异质性与宫颈癌的预后和肿瘤发生有关。

IF 4.6 2区 医学 Q2 IMMUNOLOGY
Frontiers in Cellular and Infection Microbiology Pub Date : 2025-05-13 eCollection Date: 2025-01-01 DOI:10.3389/fcimb.2025.1574511
Yi Guo, Yuhang Xiao, Changyi Zhang, Ying Wang, Guangxu Cao, Ka Yu Tse, Zhiqiang Han, Fang Li, Yong Zhi
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引用次数: 0

摘要

背景:肿瘤内微生物-宿主相互作用在癌症的发展中起着至关重要的作用。微生物组可以通过调节炎症、免疫反应和代谢途径来影响癌症的发展。因此,我们的目的是描绘景观和肿瘤内微生物群在宫颈癌(CC)中的作用。方法:采用荧光原位杂交法(FISH)证实CC组织中存在细菌群落。然后用16s rRNA和RNA-Seq来表征肿瘤内微生物群的组成。结合肿瘤肿瘤基因组图谱(TCGA)的宫颈鳞状细胞癌(CESC)数据,进一步分析肿瘤内微生物群和DEGs的临床特征。最后,通过体外实验验证了上调纤维蛋白原β链(FGB)表达片段肽对肿瘤生物学行为的影响。结果:发现了CC肿瘤中细菌组成的异质性。假单胞菌在CC组织中富集程度最高,并按相对丰度进行分组。假单胞菌丰度较高患者的临床特征是纤维蛋白原水平较高,白细胞(WBC)和白蛋白(ALB)表达水平较低。结合我们的两个集体CC和TCGA-CESC队列的转录组数据,我们发现假单胞菌丰度与CC患者的纤维蛋白原β肽表达和更差的总生存率显著相关。体外实验表明假单胞菌可通过过表达FGB促进宫颈癌细胞增殖和迁移。结论:我们描述了CC组织中肿瘤内微生物群的组成,并确定了癌组织和非癌组织中最显著差异的细菌丰度。我们的研究结果为肿瘤内假单胞菌与CC肿瘤发生之间的关系提供了新的见解,对肿瘤微环境及其相关微生物群的深入了解可能会揭示新的潜在治疗靶点并改善临床结果。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
The intratumoral microbiota heterogenicity is related to the prognosis and tumorigenesis of cervical cancer.

Background: The intratumoral microbe-host interaction plays crucial role in the development of cancer. The microbiome can influence cancer development by modulating inflammation, immune responses and metabolic pathways. Therefore, we aim to delineate the landscape and role of intratumoral microbiota in cervical cancer (CC).

Methods: The presence of bacterial community in CC tissues was confirmed by fluorescence in situ hybridization (FISH). Then 16s rRNA and RNA-Seq were used to characterize the composition of intratumoral microbiota. Combined with cervical squamous cell carcinoma (CESC) data from the Tumor Cancer Genome Atlas (TCGA), the clinical signatures of intratumoral microbiota and DEGs were further analyzed. Finally, the effect of the up-regulated Fibrinogen beta chain (FGB) expressed fragment peptide on the biological behavior of cancer was verified in vitro.

Results: We found the composition heterogeneity of bacteria in CC tumors. Pseudomonas was most highly enriched in CC tissues and grouped according to the relative abundance level. The clinical characteristics of patients with relatively high abundance of Pseudomonas had the higher levels of fibrinogen and lower levels of white blood cell (WBC) and albumin (ALB) expression. Combining transcriptome data from the two our collective CC and TCGA-CESC cohorts, we found that Pseudomonas abundance was significantly associated with fibrinogen beta peptide expression and worse overall survival in CC patients. In vitro experiment revealed that Pseudomonas could promote the proliferation and migration of cervical cancer cells through overexpression of FGB.

Conclusions: We characterized the composition of the intratumoral microbiota in CC tissues and identified the most significantly differentially abundant bacteria between cancerous and non-cancerous tissues. Our findings provide novel insights into the relationship between intratumoral Pseudomonas and the tumorigenesis of CC. A deeper understanding of the tumor microenvironment and its associated microbiota may reveal new potential therapeutic targets and improve clinical outcomes.

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来源期刊
CiteScore
7.90
自引率
7.00%
发文量
1817
审稿时长
14 weeks
期刊介绍: Frontiers in Cellular and Infection Microbiology is a leading specialty journal, publishing rigorously peer-reviewed research across all pathogenic microorganisms and their interaction with their hosts. Chief Editor Yousef Abu Kwaik, University of Louisville is supported by an outstanding Editorial Board of international experts. This multidisciplinary open-access journal is at the forefront of disseminating and communicating scientific knowledge and impactful discoveries to researchers, academics, clinicians and the public worldwide. Frontiers in Cellular and Infection Microbiology includes research on bacteria, fungi, parasites, viruses, endosymbionts, prions and all microbial pathogens as well as the microbiota and its effect on health and disease in various hosts. The research approaches include molecular microbiology, cellular microbiology, gene regulation, proteomics, signal transduction, pathogenic evolution, genomics, structural biology, and virulence factors as well as model hosts. Areas of research to counteract infectious agents by the host include the host innate and adaptive immune responses as well as metabolic restrictions to various pathogenic microorganisms, vaccine design and development against various pathogenic microorganisms, and the mechanisms of antibiotic resistance and its countermeasures.
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