Department of Gynecology and Obstetrics, 105860The Second Affiliated Hospital of Soochow University, Suzhou, China.
Department of Obstetrics, 12461Suzhou Affiliated Hospital of Nanjing Medical University, Suzhou, China.
Cell Transplant. 2021 Jan-Dec;30:963689720975398. doi: 10.1177/0963689720975398.
To screen the differential expression cytokines (DECs) in hemolysis, elevated liver enzymes, and low platelet (HELLP) syndrome, establish its differential cytokines spectra, and provide the clues for its diagnosis and pathogenic mechanism researches. Sera from four HELLP syndrome patients and four healthy controls were detected by proteome microarray. Then the analysis of Gene Ontology (GO) enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, and protein-protein interaction (PPI) network were performed and possible hub proteins were selected out, further verified by Enzyme Linked Immunosorbent Assay (ELISA) in sera from 21 HELLP syndrome patients and 21 healthy controls. Thirty DECs were defined according to -value and fold change between HELLP group and control group. GO enrichment analysis showed that DECs were mainly involved in the regulation of inflammatory response and have relationship to growth factor binding, transmembrane receptor protein kinase, and cytokine receptor activity. Seven possible hub proteins were defined by PPI analysis, including IGFBP-3/Follistatin-like 1/FLRG/Fetuin A and MMP-13/Thrombospondin-5/Aggrecan. ELISA showed higher serum levels of Fetuin A/IGFBP-3/FLGR/MMP-13/Thrombospondin-5 in HELLP group than those in controls, while the levels of Follistatin-like 1 and Aggrecan were lower in HELLP patients (all < 0.05 or <0.01).The serological DECs spectra of HELLP syndrome was established and seven possible hub proteins that may be more closely related to the disease have been verified, providing new clues for its pathogenesis, diagnosis, and clinical treatment.
为了筛选溶血、肝酶升高和血小板减少（HELLP）综合征中的差异表达细胞因子（DECs），建立其差异细胞因子谱，并为其诊断和发病机制研究提供线索。采用蛋白质组微阵列检测 4 例 HELLP 综合征患者和 4 例健康对照者的血清。然后进行基因本体论（GO）富集分析、京都基因与基因组百科全书（KEGG）通路分析和蛋白质-蛋白质相互作用（PPI）网络分析，并选择可能的枢纽蛋白，进一步通过酶联免疫吸附试验（ELISA）在 21 例 HELLP 综合征患者和 21 例健康对照者的血清中验证。根据 HELLP 组与对照组之间的-值和倍数变化，定义了 30 个 DECs。GO 富集分析表明，DECs 主要参与炎症反应的调节，与生长因子结合、跨膜受体蛋白激酶和细胞因子受体活性有关。通过 PPI 分析定义了 7 个可能的枢纽蛋白，包括 IGFBP-3/Follistatin-like 1/FLRG/Fetuin A 和 MMP-13/Thrombospondin-5/Aggrecan。ELISA 显示，HELLP 组血清 Fetuin A/IGFBP-3/FLGR/MMP-13/Thrombospondin-5 水平高于对照组（均<0.05 或<0.01），而 Follistatin-like 1 和 Aggrecan 水平在 HELLP 患者中较低（均<0.05）。建立了 HELLP 综合征的血清 DECs 谱，并验证了 7 个可能与疾病更密切相关的枢纽蛋白，为其发病机制、诊断和临床治疗提供了新线索。
