School of Basic Medical Sciences, Xinjiang Medical University, Urumqi, 830017, China.
Xinjiang Medical University Cancer Hospital, Urumqi, 830000, China.
Sci Rep. 2024 Sep 17;14(1):21731. doi: 10.1038/s41598-024-73146-9.
Cervical cancer, a prevalent malignancy in the female reproductive tract, exhibits a high incidence. Existing evidence indicates a robust correlation between alterations in vaginal flora composition and the progression of cervical cancer. Nevertheless, there is a lack of clarity concerning the specific microorganisms within the vaginal microbiota that are linked to the onset and development of cervical cancer, as well as the mechanisms through which they exert carcinogenic effects. The 16 S ribosomal (rRNA) and metagenomic sequencing technology were used to analyze vaginal microorganisms, and screening for human papillomavirus (HPV) positive cervical cancer-associated microbial markers using fold change in mean bacterial abundance. Moreover, vaginal microenvironmental factors were detected, and the local vaginal inflammatory state in patients with cervical cancer was subjected to assay via qRT-PCR and ELISA. The hub inflammatory genes were screened by transcriptome sequencing after co-culture of bacteria and normal cervical epithelial cells, and an in vitro model was utilized to assess the impacts of inflammatory factors on cervical cancer. Both cervical cancer patients and HPV-positive patients showed significant changes in the composition of the vaginal flora, characterised by a decrease in the abundance of Lactobacillus and an increase in the abundance of a variety of anaerobic bacteria; The microbial sequencing identified Porphyromonas, Porphyromonas_asaccharolytica, and Porphyromonas_uenonis as microbial markers for HPV-associated cervical cancer. Vaginal inflammatory factors in patients with cervical cancer were overexpressed. After Porphyromonas_asaccharolytica intervention on cervical epithelial H8 cells, interleukin (IL)-1β, a hub differential gene, markedly promoted tumor-associated biological behaviors at the in vitro cytological level in cervical cancer. This study for the first demonstrated that Porphyromonas, Porphyromonas_asaccharolytica, and Porphyromonas_uenonis could serve as novel microbial markers for cervical cancer. Moreover, Porphyromonas_asaccharolytica was identified as having the ability to induce the overexpression of inflammatory genes in cervical epithelial cells to create a favorable microenvironment for the onset and development of cervical cancer. The effects of dysbacteriosis on cervical cancer were microbiologically elucidated.
宫颈癌是女性生殖道常见的恶性肿瘤,发病率较高。现有证据表明,阴道菌群组成的改变与宫颈癌的发生发展之间存在密切关系。然而,对于与宫颈癌发生和发展相关的阴道微生物群中特定微生物以及它们发挥致癌作用的机制尚不清楚。本研究采用 16S 核糖体(rRNA)和宏基因组测序技术分析阴道微生物,并采用细菌平均丰度的变化筛选人乳头瘤病毒(HPV)阳性宫颈癌相关微生物标志物。此外,还检测了阴道微环境因素,并通过 qRT-PCR 和 ELISA 检测宫颈癌患者的局部阴道炎症状态。通过细菌和正常宫颈上皮细胞共培养后进行转录组测序筛选出炎症基因的枢纽,建立体外模型评估炎症因子对宫颈癌的影响。宫颈癌患者和 HPV 阳性患者的阴道菌群组成均发生显著变化,表现为乳杆菌丰度降低和多种厌氧菌丰度增加;微生物测序鉴定出卟啉单胞菌、无蔗糖卟啉单胞菌和卟啉单胞菌属为 HPV 相关宫颈癌的微生物标志物。宫颈癌患者的阴道炎症因子呈高表达。无蔗糖卟啉单胞菌干预宫颈上皮 H8 细胞后,在体外细胞学水平上,白细胞介素(IL)-1β作为枢纽差异基因显著促进肿瘤相关生物学行为。本研究首次证明,卟啉单胞菌、无蔗糖卟啉单胞菌和卟啉单胞菌属可作为宫颈癌的新型微生物标志物。此外,无蔗糖卟啉单胞菌被鉴定为具有诱导宫颈上皮细胞中炎症基因过度表达的能力,从而为宫颈癌的发生和发展创造有利的微环境。本研究从微生物角度阐明了菌群失调对宫颈癌的影响。