Department of Critical Care Medicine, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, 216 Huansha Road, Hangzhou, 310006, Zhejiang, China.
Department of Hematology, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, 216 Huansha Road, Hangzhou, 310006, Zhejiang, China.
BMC Med Genomics. 2022 May 5;15(1):103. doi: 10.1186/s12920-022-01254-4.
This is the first study to explore the potential functions and expression patterns of RNA N6-methyladenosine (m6A) and potential related genes in preeclampsia.
We identified two m6A modification patterns through unsupervised cluster analysis and validated them by principal component analysis. We quantified the relative abundance of specific infiltrating immunocytes using single-sample gene set enrichment analysis (ssGSEA) and the Wilcoxon test. To screen hub genes related to m6A regulators, we performed weighted gene coexpression network analysis. Functional enrichment analysis was conducted for differential signalling pathways and cellular processes. Preeclampsia patients were grouped by consensus clustering based on differentially expressed hub genes and the relationship between different gene-mediated classifications and clinical features.
Two m6A clusters in preeclampsia, cluster A and cluster B, were determined based on the expression of 17 m6A modification regulators; ssGSEA revealed seven significantly different immune cell subtypes between the two clusters. A total of 1393 DEGs and nine potential m6A-modified hub genes were screened. We divided the patients into two groups based on the expression of these nine genes. We found that almost all the patients in m6A cluster A were classified into hub gene cluster 1 and that a lower gestational age may be associated with more m6A-associated events.
This study revealed that hub gene-mediated classification is consistent with m6A modification clusters for predicting the clinical characteristics of patients with preeclampsia. Our results provide new insights into the molecular mechanisms of preeclampsia.
这是第一项探索 RNA N6-甲基腺苷（m6A）及其相关基因在子痫前期中潜在功能和表达模式的研究。
我们通过无监督聚类分析确定了两种 m6A 修饰模式，并通过主成分分析进行了验证。我们使用单样本基因集富集分析（ssGSEA）和 Wilcoxon 检验量化了特定浸润免疫细胞的相对丰度。为了筛选与 m6A 调节因子相关的枢纽基因，我们进行了加权基因共表达网络分析。对差异信号通路和细胞过程进行了功能富集分析。根据差异表达的枢纽基因对子痫前期患者进行共识聚类分组，并分析不同基因介导的分类与临床特征之间的关系。
基于 17 个 m6A 修饰调节因子的表达，确定了子痫前期中的两个 m6A 簇，簇 A 和簇 B；ssGSEA 揭示了两个簇之间七种显著不同的免疫细胞亚群。共筛选出 1393 个差异表达基因和 9 个潜在的 m6A 修饰枢纽基因。我们根据这九个基因的表达将患者分为两组。我们发现 m6A 簇 A 中的几乎所有患者都被归类为枢纽基因簇 1，并且较低的胎龄可能与更多的 m6A 相关事件有关。
本研究揭示了枢纽基因介导的分类与 m6A 修饰簇一致，可用于预测子痫前期患者的临床特征。我们的研究结果为子痫前期的分子机制提供了新的见解。
