Integrative analysis of transcriptomic data for the identification of biomarkers associated with T-cell activation in preterm birth

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 the PTB followed by protective treatments is essential to reduce neonatal adverse outcomes. However, due to the redundant nature of clinical conditions with other diseases, PTB-associated clinical parameters are poor predictors of the PTB. It has been thus needed to identify molecular biomarkers with high accuracy in diagnosis of PTB. Here, we performed mRNA sequencing analysis of PTB patients and full-term birth (FTB) controls in Korean population and identified differentially expressed genes (DEGs) between PTB and FTB, as well as cellular pathways represented by the DEGs. By integrating two previous gene expression profiles generated from different ethnic groups, we then identified the core T-cell activation pathway associated with the PTB, which was shared among all previous datasets, and selected the three representative DEGs (CYLD, TFRC, and RIPK2) of the core pathway as biomarker candidates for the PTB. We finally confirmed the dysregulations of the biomarker candidates and the core T-cell activation pathway in an independent cohort. Our results suggest that CYLD, TFRC, and RIPK2 can serve as reliable biomarkers for the PTB. Total RNA expression profiles of 5 full-term birth controls (FTB) and 5 preterm birth patients (PTB) were examined by Illumina NextSeq500.