Screening and analysis of plasma differential lncRNA/mRNA in early pregnancy of preeclampsia

Xin ZHANG^1,2,4#, Ning YANG^5#, Jie LU^1,3#, Yan-yan TAO⁶, Xiulong NIU², Wei CAI^2,4, Shaobo CHEN^2,4, Yuming LI¹

1. Clinical School of Cardiovascular Disease, Tianjin Medical University, Tianjin, 300457, China
2. Department of Cardiology, Characteristic Medical Center of the Chinese People’s Armed Police Force. Tianjin,300162, China
3. Department of Cardiopulmonary Function, Tianjin Cancer Hospital Airport Hospital, Tianjin 300308, China
4. Tianjin Key Laboratory of Cardiovascular Remodeling and Target Organ Injury, Tianjin,300162, China
5. Department of Hypertension, Tianjin Kanghui Hospital, Tianjin 300380, China
6. Department of Clinical Laboratory, Haihe Hospital, Tianjin University. Tianjin,300350, China

• Correspondence: Xin ZHANG, Ning YANG and Jie LU contributed to this article equally as first authors; chensbwj@126.com & cardiology2023@126.com

Abstract
Objectives
This study aimed to characterise the expression profiles of long non-coding RNA (lncRNA) and messenger RNA (mRNA) in plasma samples from individuals with preeclampsia (PE) during early pregnancy (7–14 weeks of gestation). We sought to identify key signalling pathways and biological functions linked to these transcripts and evaluate their potential for early PE diagnosis and therapeutic intervention.
Methods
From January to June 2019, we analysed frozen plasma samples from eight PE patients and eight normotensive pregnant women matched for gestational age. Transcriptome sequencing was performed using the Illumina HiSeq 4000 platform. Differentially expressed lncRNAs and mRNAs were identified with thresholds of |fold change (FC)| ≥ 2 and P ≤ 0.05. Functional enrichment analyses (Gene Ontology [GO] and Kyoto Encyclopedia of Genes and Genomes [KEGG]) were conducted to elucidate associated pathways, and a lncRNA-mRNA coexpression network was constructed to explore regulatory interactions.
Results
We identified 361 significantly dysregulated lncRNAs (171 up- and 190 down-regulated) and 3,798 mRNAs (3,320 up- and 478 down-regulated). Top dysregulated transcripts included ENST00000440816 (lncRNA, log2FC = +175.29) and TEX35 (mRNA, log2FC = +8.70). Gene Ontology analysis revealed enrichment in inflammatory response, cell adhesion, and transferase activity, while Kyoto Encyclopedia of Genes and Genomes pathways implicated phosphoinositide 3-kinase-protein kinase B, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), and mechanistic target of rapamycin (mTOR) signalling. Coexpression networks highlighted strong associations between dysregulated transcripts and oxidative stress/inflammatory processes.
Conclusion
Early-pregnancy plasma lncRNAs and mRNAs are markedly dysregulated in PE and correlate with pathogenic pathways. Notably, lncRNAs with |log2FC| ≥ 5 and mRNAs with |log2FC| ≥ 6 may serve as novel biomarkers for early PE prediction.

Keywords: preeclampsia; lncRNA; mRNA; screening; analysis; pregnancy; women health