供体circFOXN2和circNECTIN3的双环状RNA特征可预测肝移植后的早期移植物功能障碍。
A two-circular RNA signature of donor circFOXN2 and circNECTIN3 predicts early allograft dysfunction after liver transplantation.
作者信息
Wang Kun, Wei Xuyong, Wei Qiang, Lu Di, Li Wangyao, Pan Binhua, Chen Junli, Xie Haiyang, Zheng Shusen, Xu Xiao
机构信息
Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China.
Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou 310003, China.
出版信息
Ann Transl Med. 2020 Feb;8(4):94. doi: 10.21037/atm.2019.12.132.
BACKGROUND
Early allograft dysfunction (EAD) following liver transplantation is associated with poor recipient and graft survival. In recent years, circular RNAs (circRNAs) have emerged as important components of endogenous RNAs. This study aims to explore the expression profile and predictive value of graft circular RNAs for EAD after liver transplantation.
METHODS
RNA sequencing was conducted to identify the circRNA profile in donor liver tissues. Furthermore, quantitative real-time polymerase chain reaction (qRT-PCR) was used to identify candidate circRNAs. A novel model combining circular RNA signature was established to predict EAD based on the multivariate analysis.
RESULTS
A total of 442 circRNAs were differentially expressed between the EAD and non-EAD groups, of which, 223 were significantly upregulated and 219 were downregulated in the EAD group (Fold change >2, P<0.05). qRT-PCR validation indicated that circFOXN2 and circNECTIN3 levels in the EAD group were significantly lower than those in the non-EAD group (P=0.038, 0.024, respectively; n=115). Among the 115 recipients, 32 recipients with high circFOXN2 expression were classified as circular RNA signature A and the rest recipients with low circFOXN2 expression were categorized into circular RNA signature B (n=33, high circNECTIN3 expression) and C (n=50, low circNECTIN3 expression). The incidence rates of EAD in signature A, B and C were significantly different (3.1%, 21.2% and 42.0%, respectively; P=0.000). According to the multivariate analysis, a novel predictive model for EAD was developed based on CIT (P=0.000) and circular RNA signature (P=0.013). The novel model displayed a high predictive value for EAD with areas under the curve (AUC) of 0.870 (95% CI: 0.797-0.942).
CONCLUSIONS
Donor circFOXN2 and circNEXTIN3 were associated with the incidence of EAD. The novel model combing the two-circular RNA signature had a high predictive value for EAD.
背景
肝移植后的早期移植物功能障碍（EAD）与受体和移植物的不良生存相关。近年来，环状RNA（circRNA）已成为内源性RNA的重要组成部分。本研究旨在探讨肝移植后移植物环状RNA对EAD的表达谱及预测价值。
方法
进行RNA测序以鉴定供体肝组织中的circRNA谱。此外，采用定量实时聚合酶链反应（qRT-PCR）来鉴定候选circRNA。基于多变量分析建立了一种结合环状RNA特征的新型模型来预测EAD。
结果
EAD组和非EAD组之间共有442种circRNA差异表达，其中EAD组中有223种显著上调，219种下调（倍数变化>2，P<0.05）。qRT-PCR验证表明，EAD组中circFOXN2和circNECTIN3水平显著低于非EAD组（分别为P=0.038、0.024；n=115）。在115名受体中，32名circFOXN2表达高的受体被分类为环状RNA特征A，其余circFOXN2表达低的受体被分为环状RNA特征B（n=33，circNECTIN3表达高）和C（n=50，circNECTIN3表达低）。特征A、B和C中EAD的发生率显著不同（分别为3.1%、21.2%和42.0%；P=0.000）。根据多变量分析，基于CIT（P=0.000）和环状RNA特征（P=0.013）建立了一种新型的EAD预测模型。该新型模型对EAD显示出较高的预测价值，曲线下面积（AUC）为0.870（95%CI：0.797-0.942）。
结论
供体circFOXN2和circNEXTIN3与EAD的发生率相关。结合双环状RNA特征的新型模型对EAD具有较高的预测价值。
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