H3K27me3在血管瘤及血管畸形中的表达及临床意义

Expression and clinical significance of H3K27me3 in hemangioma and vascular malformation

目的探讨内皮细胞H3K27me3在血管瘤和血管畸形中的表达及临床意义。方法收集2010年1月至2021年6月福建医科大学附属第一医院病理科244例血管瘤和血管畸形患者库存蜡块,采用免疫组化SP法检测H3K27me3表达水平,分析H3K27me3在血管瘤和血管畸形中的表达差异,通过生物信息学分析并结合血管周细胞SMA染色的结果探讨其在血管异常发育中的潜在作用,应用ROC曲线评价其在血管瘤和血管畸形鉴别中的诊断价值。结果H3K27me3主要在血管瘤的内皮细胞表达,其在血管瘤的平均表达率为50%~90%,但血管畸形内皮细胞H3K27me3表达率为30%~50%,血管周细胞几乎不表达。基于GSE21212数据集并结合文献获得内皮细胞限制性表达基因10个,通过ENCODE网页工具分析发现不同谱系内皮细胞SOX2启动子区有H3K27me3富集,H3K27me3与SOX2交互作用可能与血管的发育和分化有关。结论内皮细胞H3K27me3可以作为血管瘤与血管畸形鉴别的补充标记物,但其在婴儿的血管瘤中表达具有异质性。

ObjectiveTo investigate the expression and clinical significance of H3K27me3 in vascular hemangioma and malformation.MethodsParaffin-embedded tissue blocks from 244 patients with hemangioma and vascular malformation admitted in our hospital from January 2010 and June 2021 were collected.The expression levels of H3K27me3 and smooth muscle actin(SMA)in vascular endothelial and perivascular cells were detected by immunohistochemical SP assay,and its expression differences between hemangioma and vascular malformation was analyzed.Bioinformatics analysis was further applied to explore its potential role in anigodysplasia in combination of the results of SMA immunostaining.Receiver operating characteristic(ROC)curve was drawn to evaluate its diagnostic value in differentiation of hemangioma and vascular malformation.ResultsIn vascular hemangioma,H3K27me3 expression was mainly restricted to vascular endothelial cells,with an expression rate of 50%~90%.However,in vascular malformations,it was expressed in vascular endothelial cells,with an expression rate of 30%~50%,and lost in perivascular cells.There were top 10 endothelium restricted genes derived from GSE21212 dataset based on concerning literatures.According to ChIP-seq data from ENCODE website,H3K27me3 was enriched in the SOX2 promoter of different endothelium lineages,and the molecular interaction of H3K27me3 and SOX2 may be associated with vessel development and differentiation.ConclusionThe expression of H3K27me3 in vascular endothelial cells can be used as a candidate marker to distinguish hemangioma and vascular malformation.However,its expression in infantile hemangioma is immunologically heterogeneous.