Shen Zhonghua, Gong Weihua
Department of Cardiovascular Surgery, Second Affiliated Hospital of School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China (mainland).
Department of Surgery, Second Affiliated Hospital of School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China (mainland).
Ann Transplant. 2015 Jun 5;20:312-9. doi: 10.12659/AOT.893029.
Cardiac allograft rejection (AR) can cause graft dysfunction and even mortality, and an early noninvasive diagnosis of cardiac AR is required. This study aims to identify candidate biomarkers in peripheral blood for cardiac AR, which might benefit early diagnosis.
Gene expression profile (ID: GSE5967) of peripheral blood from cardiac allograft recipients was achieved from the Gene Expression Omnibus database, including 7 chips in rejection group, 7 chips in post-rejection group, and 7 chips in control group. After data preprocessing, limma package was used to screen the differentially expressed genes (DEGs) between these groups (|log2 fold change| ≥0.58, and p-value <0.05). Then, online software DAVID was utilized to study the pathways and functions involving these DEGs (p-value <0.05).
Totally, 21 up-regulated and 16 down-regulated DEGs were identified between rejection and control groups, and up-regulated DEGs were mainly enriched in bio-functions about translation and ribosome. Furthermore, 3 up-regulated and 14 down-regulated DEGs were identified between post-rejection and control groups. The down-regulated DEGs in 2 contrast groups were mainly enriched in bio-functions about lipid biosynthesis and membrane.
RPL7, RPL11, RPS23, RPS25, SCD5, CSF3R, and FPR1 were predicted as candidate biomarkers in peripheral blood for monitoring cardiac AR. The up-regulation of RPL7, RPS25, RPS23, and RPL11 might promote the translation of AR-related cytokines, and the down-regulation of SCD5, CSF3R, and FPR1 might reduce the stability of cell membrane, mediating cytokines secretion and the phagocytosis of macrophages. However, further studies are required to validate these predictions.
心脏移植排斥反应（AR）可导致移植心脏功能障碍甚至死亡，因此需要对心脏AR进行早期无创诊断。本研究旨在识别外周血中用于心脏AR的候选生物标志物，这可能有助于早期诊断。
从基因表达综合数据库获取心脏移植受者外周血的基因表达谱（ID：GSE5967），包括排斥反应组7个芯片、排斥反应后组7个芯片和对照组7个芯片。经过数据预处理后，使用limma软件包筛选这些组之间的差异表达基因（DEGs）（|log2倍数变化|≥0.58，且p值<0.05）。然后，利用在线软件DAVID研究涉及这些DEGs的通路和功能（p值<0.05）。
在排斥反应组和对照组之间共鉴定出21个上调和16个下调的DEGs，上调的DEGs主要富集在翻译和核糖体相关的生物学功能中。此外，在排斥反应后组和对照组之间鉴定出3个上调和14个下调的DEGs。两个对比组中下调的DEGs主要富集在脂质生物合成和膜相关的生物学功能中。
RPL7、RPL11、RPS23、RPS25、SCD5、CSF3R和FPR1被预测为外周血中监测心脏AR的候选生物标志物。RPL7、RPS25、RPS23和RPL11的上调可能促进AR相关细胞因子的翻译，而SCD5、CSF3R和FPR1的下调可能降低细胞膜稳定性，介导细胞因子分泌和巨噬细胞吞噬作用。然而，需要进一步研究来验证这些预测。
