Department of Hospital Infection Control, First Hospital of Quanzhou Affiliated to Fujian Medical University, Quanzhou, China.
Department of Epidemiology and Health Statistics, Fujian Provincial Key Laboratory of Environment Factors and Cancer, School of Public Health, Fujian Medical University, Fuzhou, China.
Int J Cancer. 2021 Apr 1;148(7):1708-1716. doi: 10.1002/ijc.33428. Epub 2020 Dec 31.
The underlying molecular mechanisms involved in the pathogenesis of endometrial cancer (EC) are still not well understood. Our goal was to investigate the composition of the endometrial microbiota and the association with inflammatory cytokines in EC. Endometrial microbiota profiles of women with EC (n = 25) and benign uterine lesions (BUL, n = 25) were assessed by 16S ribosomal RNA gene amplicon sequencing. The expression levels of interleukin-6 (IL-6), interleukin-8 (IL-8), and interleukin-17 (IL-17) mRNA and protein in the endometrial tissues of the two groups were determined by real-time quantitative polymerase chain reaction and Western blot, respectively. There were significant differences in alpha diversity based on the observed operational taxonomic units (P = .002), Pielou evenness (P = .001), and Shannon index (P < .001) between EC and BUL groups. Significant differences were also found in Bray-Curtis (P = .001) and unweighted UniFrac (P = .001) beta diversity measures between the two groups. At the genus level, Micrococcus was more abundant in the EC group. Pseudoramibacter_Eubacterium, Rhodobacter, Vogesella, Bilophila, Rheinheimera, and Megamonas were enriched in the BUL group. There were no differences in IL-8 and IL-17 protein levels between the two groups, except IL-6 protein levels. However, the mRNA expression levels of IL-6, IL-8, and IL-17 were significantly different. Moreover, the relative abundances of Micrococcus was positively correlated with IL-6, and IL-17 mRNA levels. In conclusion, our results suggested that dysbiosis of endometrial microbiota and the inflammatory cytokines were associated with Micrococcus in EC patients, which might be useful for exploration of the mechanism between the endometrial microbiota and inflammatory responses in future studies.
子宫内膜癌（EC）发病机制中涉及的潜在分子机制尚不清楚。我们的目标是研究 EC 患者子宫内膜微生物组的组成及其与炎症细胞因子的关联。通过 16S 核糖体 RNA 基因扩增子测序评估了 25 例 EC 患者和 25 例良性子宫病变（BUL）患者的子宫内膜微生物组谱。通过实时定量聚合酶链反应和 Western blot 分别测定两组子宫内膜组织中白细胞介素-6（IL-6）、白细胞介素-8（IL-8）和白细胞介素-17（IL-17）mRNA 和蛋白的表达水平。EC 组和 BUL 组之间基于观察到的操作分类单位（P =.002）、Pielou 均匀度（P =.001）和 Shannon 指数（P <.001）的 alpha 多样性存在显著差异。两组之间 Bray-Curtis（P =.001）和无权重 UniFrac（P =.001）β多样性测量也存在显著差异。在属水平上，EC 组中 Micrococcus 更为丰富。Pseudoramibacter_Eubacterium、Rhodobacter、Vogesella、Bilophila、Rheinheimera 和 Megamonas 在 BUL 组中富集。两组间 IL-8 和 IL-17 蛋白水平无差异，除 IL-6 蛋白水平外。然而，IL-6、IL-8 和 IL-17 的 mRNA 表达水平存在显著差异。此外，Micrococcus 的相对丰度与 IL-6 和 IL-17 mRNA 水平呈正相关。综上所述，我们的结果表明，EC 患者子宫内膜微生物组失调和炎症细胞因子与 Micrococcus 有关，这可能有助于未来研究中探索子宫内膜微生物组与炎症反应之间的机制。
