Development and validation of a transcriptomic signature-based model as the predictive, preventive, and personalized medical strategy for preterm birth within 7 days in threatened preterm labor women

Yuxin Ran; Jie He; Wei Peng; Zheng Liu; Youwen Mei; Yunqian Zhou; Nanlin Yin; Hongbo Qi

doi:10.1007/s13167-021-00268-9

Development and validation of a transcriptomic signature-based model as the predictive, preventive, and personalized medical strategy for preterm birth within 7 days in threatened preterm labor women

EPMA J. 2022 Jan 18;13(1):87-106. doi: 10.1007/s13167-021-00268-9. eCollection 2022 Mar.

Authors

Yuxin Ran^{1

2

3

4}, Jie He^{1

3

4}, Wei Peng^{1

3

4}, Zheng Liu^{1

3

4}, Youwen Mei^{1

3

4}, Yunqian Zhou^{1

3

4}, Nanlin Yin^{1

3

4

5}, Hongbo Qi^{2

3

4}

Affiliations

¹ Department of Obstetrics, The First Affiliated Hospital of Chongqing Medical University, No.1 Youyi Rd, Yuzhong District, Chongqing, 400016 China.
² Chongqing Health Center for Women and Children, No. 120 Longshan Road, Yubei District, Chongqing, 401120 China.
³ Chongqing Key Laboratory of Maternal and Fetal Medicine, Chongqing Medical University, No. 1 Yixueyuan Rd, Yuzhong District, Chongqing, 400016 China.
⁴ Joint International Research Laboratory of Reproduction and Development of Chinese Ministry of Education, Chongqing Medical University, No. 1 Yixueyuan Rd, Yuzhong District, Chongqing, 400016 China.
⁵ Center for Reproductive Medicine, The First Affiliated Hospital of Chongqing Medical University, No.1 Youyi Rd, Yuzhong District, Chongqing, 400016 China.

Abstract

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.

Keywords: Clinical feasibility; Improved individual outcomes; Inflammatory activation; Molecular patterns; Predictive preventive and personalized medicine (PPPM/3PM); Preterm birth.