lancet-header

Preprints with The Lancet is part of SSRN´s First Look, a place where journals identify content of interest prior to publication. Authors have opted in at submission to The Lancet family of journals to post their preprints on Preprints with The Lancet. The usual SSRN checks and a Lancet-specific check for appropriateness and transparency have been applied. Preprints available here are not Lancet publications or necessarily under review with a Lancet journal. These preprints are early stage research papers that have not been peer-reviewed. The findings should not be used for clinical or public health decision making and should not be presented to a lay audience without highlighting that they are preliminary and have not been peer-reviewed. For more information on this collaboration, see the comments published in The Lancet about the trial period, and our decision to make this a permanent offering, or visit The Lancet´s FAQ page, and for any feedback please contact preprints@lancet.com.

PIWI-Interacting RNA Sequencing Profiles in Maternal Plasma-Derived Exosomes Reveal Novel Non-Invasive Prenatal Biomarkers for the Diagnosis of Nonsyndromic Cleft Lip and Palate

36 Pages Posted: 14 Oct 2020

See all articles by Shanshan Jia

Shanshan Jia

China Medical University - Key Laboratory of Health Ministry for Congenital Malformation

Qiang Zhang

China Medical University - Key Laboratory of Health Ministry for Congenital Malformation

Yu Wang

China Medical University - Key Laboratory of Health Ministry for Congenital Malformation

Yanfu Wang

China Medical University - Key Laboratory of Health Ministry for Congenital Malformation

Dan Liu

China Medical University - Key Laboratory of Health Ministry for Congenital Malformation

Yiwen He

China Medical University - Key Laboratory of Health Ministry for Congenital Malformation

Xiaowei Wei

China Medical University - Key Laboratory of Health Ministry for Congenital Malformation

Hui Gu

China Medical University - Key Laboratory of Health Ministry for Congenital Malformation

Wei Ma

China Medical University - Key Laboratory of Health Ministry for Congenital Malformation

Wenting Luo

China Medical University - Key Laboratory of Health Ministry for Congenital Malformation

Zhengwei Yuan

China Medical University - Key Laboratory of Health Ministry for Congenital Malformation

More...

Abstract

Background: Nonsyndromic cleft lip and palate (nsCLP) is a common birth defect with high neonatal morbidity/mortality and complex etiology. Current clinical strategies to diagnose this disorder mainly rely on ultrasound with some limitations. Therefore, we firstly investigated PIWI-interacting RNAs (piRNAs) as potential prenatal biomarkers in plasma-derived exosomes from pregnant women carrying nsCLP fetuses.

Methods: In total, 252 pregnant women, including 50 pregnant women carrying nsCLP fetuses, 40 pregnant women carrying fetuses with congenital heart defects (CHDs), 21 pregnant women carrying fetuses with neural tube defects (NTDs), and 141 healthy participants were selected from an ongoing Shengjing Birth Cohort Study. Small RNA sequencing in plasma-derived exosomes was used to analyze five pregnant women carrying nsCLP fetuses and five pregnant women carrying normal fetuses.

Findings: We identified a biomarker panel consisting of these three pregnancy-associated exosomal piRNAs (hsa-piR-009228, hsa-piR-016659, and hsa-piR-020496) for distinguishing nsCLP from controls (area under the receiver operating characteristic curve, 0.950; P < 0.0001). They were also significantly downregulated in plasma exosomes from pregnant women carrying NTDs fetuses (P < 0.0001). In addition, hsa-piR-009228 was downregulated, whereas hsa-piR-016659 was upregulated in plasma exosomes from pregnant women carrying CHDs fetuses.

Interpretation: Our work highlights the potential clinical application value of piRNAs in predicting the nonsyndromic cleft lip and palate, neural tube defects and congenital heart defects.

Funding: This work was supported by the National Key Research and Development Program (2016YFC1000505), the National Natural Science Foundation of China (Grant numbers: 81871219, 81671469), and the LiaoNing Revitalization Talents Program (XLYC1902099).

Declaration of Interests: The authors declare that they have no interests that might be perceived as posing conflict or bias.

Ethics Approval Statement: Written informed consent was obtained from all pregnant women, and the study was performed in accordance with the principles of the Declaration of Helsinki and approved by the Ethics Committee of Shengjing Hospital Affiliated to China Medical University (approval no. 2017PS264K).

Keywords: Biomarker, congenital heart defect, exosomes, neural tube defect, nonsyndromic cleft lip and palate, PIWI-interacting RNA, plasma, prenatal diagnosis

Suggested Citation

Jia, Shanshan and Zhang, Qiang and Wang, Yu and Wang, Yanfu and Liu, Dan and He, Yiwen and Wei, Xiaowei and Gu, Hui and Ma, Wei and Luo, Wenting and Yuan, Zhengwei, PIWI-Interacting RNA Sequencing Profiles in Maternal Plasma-Derived Exosomes Reveal Novel Non-Invasive Prenatal Biomarkers for the Diagnosis of Nonsyndromic Cleft Lip and Palate. Available at SSRN: https://ssrn.com/abstract=3677882 or http://dx.doi.org/10.2139/ssrn.3677882

Shanshan Jia

China Medical University - Key Laboratory of Health Ministry for Congenital Malformation ( email )

Qiang Zhang

China Medical University - Key Laboratory of Health Ministry for Congenital Malformation

Yu Wang

China Medical University - Key Laboratory of Health Ministry for Congenital Malformation

Yanfu Wang

China Medical University - Key Laboratory of Health Ministry for Congenital Malformation ( email )

Dan Liu

China Medical University - Key Laboratory of Health Ministry for Congenital Malformation

Yiwen He

China Medical University - Key Laboratory of Health Ministry for Congenital Malformation

Xiaowei Wei

China Medical University - Key Laboratory of Health Ministry for Congenital Malformation ( email )

Hui Gu

China Medical University - Key Laboratory of Health Ministry for Congenital Malformation

Wei Ma

China Medical University - Key Laboratory of Health Ministry for Congenital Malformation

Wenting Luo

China Medical University - Key Laboratory of Health Ministry for Congenital Malformation

Zhengwei Yuan (Contact Author)

China Medical University - Key Laboratory of Health Ministry for Congenital Malformation ( email )

Shenyang
China