Integrative analysis of transcriptomic data for identification of T-cell activation-related mRNA signatures indicative of preterm birth

Jae Young Yoo,Daye Kim,Daehee Hwang,Do Young Hyeon,Yourae Shin,Young Ju Kim,Young-Ah You,Soo Min Kim

doi:10.1038/s41598-021-81834-z

Jae Young Yoo, Daye Kim + Show 6 more

Open Access

https://doi.org/10.1038/s41598-021-81834-z

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Abstract

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.

Highlights

Preterm birth (PTB) is the birth of a baby at less than 37 weeks of gestation, as opposed to the usual about 40 weeks, called full term birth (FTB)[1]
Singleton pregnant women diagnosed with preterm labor (PTL) and/or premature preterm rupture of membranes were included as PTB patients in the cohorts
Age, parity, and gravidity showed no significant differences between PTB patients and full-term birth (FTB) controls while gestational age, birth weight, and APGAR scores (1 and 5 min) are significantly different

Summary

Introduction

Preterm birth (PTB) is the birth of a baby at less than 37 weeks of gestation, as opposed to the usual about 40 weeks, called full term birth (FTB)[1]. Long-term problems include increased risk of hypertension, type 2 diabetes, cardiovascular disease, chronic kidney disease, asthma, and neurocognitive d isorders[6,7,8] Owing to these adverse outcomes, it is important to diagnose PTB as early as possible, followed by protective interventions. Heng et al.[13] compared the gene expression profiles of whole blood samples from 75 Australian PTB patients and 79 full-term birth (FTB) controls. We initially performed mRNA sequencing analysis in five Korean PTB patients and five FTB controls and identified the differentially expressed genes (DEGs) between them. These DEGs, and the cellular pathways enriched by them may serve as candidate predictors for PTB in the Korean population. We confirmed the dysregulation of the selected candidates and the shared pathway in an independent cohort of 83 Korean PTB patients and 113 FTB controls, to support the validity of the PTB predictor candidates

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