血管瘤血清标志物血管生长素的体外干预实验及临床应用研究

Hemangioma, the most common tumor of infancy, is affecting up to 1% of liveborn babies. Currently, oral propranolol therapy have significant effect on severe cases. Clinically, because of the lack of method to evaluate their proliferative potency, over-treatment may lead to severe iatrogenic appearance defect and systemic adverse reactions. Hence, the discovery of potential useful serum markers to evaluate proliferative potency and therapeutic prognosis of hemangiomas remains a high priority. Unfortunately, to our knowledge, no study has yet discovered an useful serum marker, although there are distinct serology abnormalities.To search a potential serum marker for clinical monitoring, we firstly utilized advanced cDNA microarray to screening. Angiogenin was found out to be a potential serum marker of hemangioma, whose expressions in tissues of hemangiomas and serum of the patients were validated. Moreover, angiogenin serum levels in patients with hemangiomas correlate with the stages with high specificity(90.3%) and sensitivity(87.0%). This study of original innovation represents the first investigation examining angiogenin in infantile hemangioma. The innovation got the national patent, and this paper had been accepted by Plastic and Reconstructive Surgery . On this basis,we prepare to make use of the successful three- dimension model for angiogenesis of hemangioma and cultivante system for vascular endothelial cell of hemangioma, to analyze the dose-effect relationship between angiogenin and angiogenesis/ vascular endothelial cell proliferation of hemangioma. Meanwhile, we perform a prospective clinical application study, to analyze the clinical application value of serum angiogenin level, aiming at providing a serum monitoring factors to screening severe hemangiomas early, evaluate proliferative potency at the morning proliferative stage and therapeutic stable phase. Finally, we systematically compare the data in vitro experiments and the results of clinical monitoring .This study aims to provide a serum monitor factor for clinical, which is helpful for making decisions about hemangioma treatment method, timing and drug withdrawal time, and then improving comprehensive treatment.

血管瘤是婴幼儿最常见肿瘤，发病率高达1%，口服心得安是严重血管瘤的首选治疗，但由于瘤体增殖潜能难以预测，过度治疗可能造成严重副作用，临床上急需预测瘤体增殖潜能、辅助治疗的血清指标。血管瘤病程虽伴有血清学异常，但从未发现血清标志物。本研究组经基因芯片系统筛查及组织学血清学验证，发现新血清标志物- - 血管生长素，其血清浓度与病程相关，特异度达90.3%,敏感度达87.0%,诊断价值强。该因子在既往血管瘤研究中从未报道，属源头创新，获国家专利，论文被PRS杂志接受。在此基础上，备进一步利用已成功构建的三维血管瘤血管生成模型和细胞培养体系，分析该因子促血管生成及细胞增殖的量效关系。同时行前瞻性临床应用研究，评价该因子对早期筛查重症血管瘤、预测增生早期及治疗稳定期瘤体增殖潜能等方面的应用价值，最后系统比较体外模型干预结果和临床监测结果，旨在为临床提供血清监测因子，以辅助治疗方式、时机及停药时间的决策。

项目执行过程中，于产科收集1100例新生儿的脐血，随访所得血管瘤随访阳性率逾1.3%。口服心得安是严重血管瘤的首选治疗，但由于瘤体增殖潜能难以预测，过度治疗可能造成严重副作用，临床上急需预测瘤体增殖潜能、辅助治疗的血清指标。血管瘤病程虽伴有血清学异常，但未发现血清标志物。本研究组经基因芯片系统筛查及组织学血清学验证，发现新血清标志物——血管生长素，其血清浓度与病程相关，特异度达90.3%,敏感度达87.0%,诊断价值强。该因子在既往血管瘤研究中从未报道，属源头创新，获国家发明专利，论文被PRS 杂志接受。在此基础上，利用成功构建的血管瘤干性细胞培养体系，分析该因子促血管生成及细胞增殖的量效关系。同时行前瞻性临床应用研究，评价早期筛查重症血管瘤、预测增生早期及治疗稳定期瘤体增殖潜能等方面的应用价值。最后，结合蛋白定量质谱（SWATH）分析血浆中蛋白表达情况，系统比较体外模型干预结果和临床监测结果，旨在为临床提供血清监测因子，以辅助治疗方式、时机及停药时间的决策。