Ran Yuxin, He Jie, Peng Wei, Liu Zheng, Mei Youwen, Zhou Yunqian, Yin Nanlin, Qi Hongbo
Department of Obstetrics, The First Affiliated Hospital of Chongqing Medical University, No.1 Youyi Rd, Yuzhong District, Chongqing, 400016 China.
Chongqing Health Center for Women and Children, No. 120 Longshan Road, Yubei District, Chongqing, 401120 China.
EPMA J. 2022 Jan 18;13(1):87-106. doi: 10.1007/s13167-021-00268-9. eCollection 2022 Mar.
Preterm birth (PTB) is the leading cause of neonatal death. The essential strategy to prevent PTB is the accurate identification of threatened preterm labor (TPTL) women who will have PTB in a short time (< 7 days). Here, we aim to propose a clinical model to contribute to the effective prediction, precise prevention, and personalized medical treatment for PTB < 7 days in TPTL women through bioinformatics analysis and prospective cohort studies. In this study, the 1090 key genes involved in PTB < 7 days in the peripheral blood of TPTL women were ascertained using WGCNA. Based on this, the biological basis of immune-inflammatory activation (e.g., IFNγ and TNFα signaling) as well as immune cell disorders (e.g., monocytes and Th17 cells) in PTB < 7 days were revealed. Then, four core genes (JOSD1, IDNK, ZMYM3, and IL1B) that best represent their transcriptomic characteristics were screened by SVM and LASSO algorithm. Therefore, a prediction model with an AUC of 0.907 was constructed, which was validated in a larger population (AUC = 0.783). Moreover, the predictive value (AUC = 0.957) and clinical feasibility of this model were verified through the clinical prospective cohort we established. In conclusion, in the context of Predictive, Preventive, and Personalized Medicine (3PM), we have developed and validated a model to predict PTB < 7 days in TPTL women. This is promising to greatly improve the accuracy of clinical prediction, which would facilitate the personalized management of TPTL women to precisely prevent PTB < 7 days and improve maternal-fetal outcomes.
早产(PTB)是新生儿死亡的主要原因。预防PTB的关键策略是准确识别短期内(<7天)即将发生PTB的先兆早产(TPTL)妇女。在此,我们旨在通过生物信息学分析和前瞻性队列研究,提出一种临床模型,以有助于对TPTL妇女中<7天的PTB进行有效预测、精准预防和个性化医疗。在本研究中,使用WGCNA确定了TPTL妇女外周血中与<7天PTB相关的1090个关键基因。在此基础上,揭示了<7天PTB中免疫炎症激活(如IFNγ和TNFα信号通路)以及免疫细胞紊乱(如单核细胞和Th17细胞)的生物学基础。然后,通过支持向量机(SVM)和套索(LASSO)算法筛选出最能代表其转录组特征的四个核心基因(JOSD1、IDNK、ZMYM3和IL1B)。因此,构建了一个曲线下面积(AUC)为0.907的预测模型,并在更大的人群中进行了验证(AUC = 0.783)。此外,通过我们建立的临床前瞻性队列验证了该模型的预测价值(AUC = 0.957)和临床可行性。总之,在预测、预防和个性化医学(3PM)的背景下,我们开发并验证了一种模型,用于预测TPTL妇女中<7天的PTB。这有望大大提高临床预测的准确性,从而有助于对TPTL妇女进行个性化管理,以精准预防<7天的PTB并改善母婴结局。