Circulating trophoblast cell clusters for early detection of placenta accreta spectrum disorders

循环滋养层细胞簇用于胎盘植入谱系疾病的早期检测

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作者:Yalda Afshar # ,Jiantong Dong # ,Pan Zhao ,Lei Li ,Shan Wang ,Ryan Y Zhang ,Ceng Zhang ,Ophelia Yin ,Christina S Han ,Brett D Einerson ,Tania L Gonzalez ,Huirong Zhang ,Anqi Zhou ,Zhuo Yang ,Shih-Jie Chou ,Na Sun ,Ju Cheng ,Henan Zhu ,Jing Wang ,Tiffany X Zhang ,Yi-Te Lee ,Jasmine J Wang ,Pai-Chi Teng ,Peng Yang ,Dongping Qi ,Meiping Zhao ,Myung-Shin Sim ,Ruilian Zhe ,Jeffrey D Goldstein ,John Williams 3rd ,Xietong Wang ,Qingying Zhang ,Lawrence D Platt ,Chang Zou ,Margareta D Pisarska ,Hsian-Rong Tseng ,Yazhen Zhu

Abstract

Placenta accreta spectrum (PAS) is a high-risk obstetrical condition associated with significant morbidity and mortality. Current clinical screening modalities for PAS are not always conclusive. Here, we report a nanostructure-embedded microchip that efficiently enriches both single and clustered circulating trophoblasts (cTBs) from maternal blood for detecting PAS. We discover a uniquely high prevalence of cTB-clusters in PAS and subsequently optimize the device to preserve the intactness of these clusters. Our feasibility study on the enumeration of cTBs and cTB-clusters from 168 pregnant women demonstrates excellent diagnostic performance for distinguishing PAS from non-PAS. A logistic regression model is constructed using a training cohort and then cross-validated and tested using an independent cohort. The combined cTB assay achieves an Area Under ROC Curve of 0.942 (throughout gestation) and 0.924 (early gestation) for distinguishing PAS from non-PAS. Our assay holds the potential to improve current diagnostic modalities for the early detection of PAS.

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