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。
The intratumoral microbiota heterogenicity is related to the prognosis and tumorigenesis of cervical cancer.
作者信息
Guo Yi, Xiao Yuhang, Zhang Changyi, Wang Ying, Cao Guangxu, Tse Ka Yu, Han Zhiqiang, Li Fang, Zhi Yong
机构信息
Department of Gynecology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China.
Department of Obstetrics and Gynecology, National Clinical Research Center for Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
出版信息
Front Cell Infect Microbiol. 2025 May 13;15:1574511. doi: 10.3389/fcimb.2025.1574511. eCollection 2025.
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 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
RESULTS
We found the composition heterogeneity of bacteria in CC tumors. 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 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 abundance was significantly associated with fibrinogen beta peptide expression and worse overall survival in CC patients. experiment revealed that 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 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.
背景
肿瘤内微生物与宿主的相互作用在癌症发展中起着关键作用。微生物群可通过调节炎症、免疫反应和代谢途径来影响癌症发展。因此，我们旨在描绘宫颈癌（CC）肿瘤内微生物群的概况及其作用。
方法
通过荧光杂交（FISH）确认CC组织中细菌群落的存在。然后使用16s rRNA和RNA测序来表征肿瘤内微生物群的组成。结合来自肿瘤癌症基因组图谱（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差异表达基因（DEGs）的临床特征。最后，验证上调的纤维蛋白原β链（FGB）表达片段肽对癌症生物学行为的影响。
结果
我们发现CC肿瘤中细菌组成具有异质性。在CC组织中高度富集，并根据相对丰度水平进行分组。相对丰度较高的患者临床特征为纤维蛋白原水平较高，白细胞（WBC）和白蛋白（ALB）表达水平较低。结合我们两个CC队列和TCGA - CESC队列的转录组数据，我们发现其丰度与CC患者的纤维蛋白原β肽表达及较差的总生存率显著相关。实验表明，它可通过FGB的过表达促进宫颈癌细胞的增殖和迁移。
结论
我们描绘了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之间差异最显著的丰富细菌。我们的研究结果为肿瘤内微生物群与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更深入了解可能揭示新的潜在治疗靶点并改善临床结果。
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