Department of Obstetrics and Gynecology, College of Medicine and Ewha Medical Institute, Ewha Womans University, Seoul, 07804, Republic of Korea.
School of Biological Sciences, Seoul National University, Seoul, 08826, Republic of Korea.
Sci Rep. 2021 Jan 27;11(1):2392. doi: 10.1038/s41598-021-81834-z.
Preterm birth (PTB), defined as birth at less than 37 weeks of gestation, is a major determinant of neonatal mortality and morbidity. Early diagnosis of PTB risk followed by protective interventions are essential to reduce adverse neonatal outcomes. However, due to the redundant nature of the clinical conditions with other diseases, PTB-associated clinical parameters are poor predictors of PTB. To identify molecular signatures predictive of PTB with high accuracy, we performed mRNA sequencing analysis of PTB patients and full-term birth (FTB) controls in Korean population and identified differentially expressed genes (DEGs) as well as cellular pathways represented by the DEGs between PTB and FTB. By integrating the gene expression profiles of different ethnic groups from previous studies, we identified the core T-cell activation pathway associated with PTB, which was shared among all previous datasets, and selected three representative DEGs (CYLD, TFRC, and RIPK2) from the core pathway as mRNA signatures predictive of PTB. We confirmed the dysregulation of the candidate predictors and the core T-cell activation pathway in an independent cohort. Our results suggest that CYLD, TFRC, and RIPK2 are potentially reliable predictors for PTB.
早产（PTB）定义为妊娠不足 37 周的分娩，是新生儿死亡率和发病率的主要决定因素。早期诊断 PTB 风险并采取保护干预措施对于降低不良新生儿结局至关重要。然而，由于与其他疾病的临床条件具有冗余性，PTB 相关的临床参数是 PTB 的不良预测指标。为了以高精度识别预测 PTB 的分子特征，我们对韩国人群中的 PTB 患者和足月分娩（FTB）对照进行了 mRNA 测序分析，确定了差异表达基因（DEGs）以及 DEGs 代表的细胞途径在 PTB 和 FTB 之间。通过整合来自先前研究的不同种族群体的基因表达谱，我们确定了与 PTB 相关的核心 T 细胞激活途径，该途径在所有先前的数据集中共存，并从核心途径中选择三个代表性的 DEGs（CYLD、TFRC 和 RIPK2）作为预测 PTB 的 mRNA 特征。我们在独立队列中证实了候选预测因子和核心 T 细胞激活途径的失调。我们的结果表明，CYLD、TFRC 和 RIPK2 可能是 PTB 的可靠预测因子。
