Du Mengtian, Van Ness Sarah, Gordeuk Victor, Nouraie Sayed M, Nekhai Sergei, Gladwin Mark, Steinberg Martin H, Sebastiani Paola
Department of Biostatistics, Boston University School of Public Health, 801 Massachusetts Avenue, Boston, MA 02118, United States.
Department of Biostatistics, Boston University School of Public Health, 801 Massachusetts Avenue, Boston, MA 02118, United States.
Blood Cells Mol Dis. 2018 Sep;72:1-9. doi: 10.1016/j.bcmd.2018.05.001. Epub 2018 May 16.
Identifying sickle cell disease patients at high risk of complications could lead to personalized treatment and better prognosis but despite many advances prediction of the clinical course of these patients remains elusive. We propose a system-type approach to discover profiles of multiple, common biomarkers that correlate with morbidity and mortality in sickle cell disease. We used cluster analysis to discover 17 signatures of 17 common circulating biomarkers in 2320 participants of the Cooperative Study of Sickle Cell Disease, and evaluated the association of these signatures with risk for stroke, pain, leg ulceration, acute chest syndrome, avascular necrosis, seizure, death, and trend of fetal hemoglobin and hemolysis using longitudinally collected data. The analysis shows that some of the signatures are associated with reduced risk for complications, while others are associated with increased risk for complications. We also show that these signatures repeat in two more contemporary studies of sickle cell disease and correlate with recently discovered biomarkers of pulmonary vascular disease. With replication and further study, these biomarker signatures could become an important and affordable precision medicine tool to aid treatment and management of the disease.
识别镰状细胞病并发症高危患者可实现个性化治疗并改善预后，但尽管取得了诸多进展，预测这些患者的临床病程仍然困难重重。我们提出一种系统性方法，以发现与镰状细胞病发病率和死亡率相关的多种常见生物标志物的特征。我们使用聚类分析在2320名镰状细胞病合作研究参与者中发现了17种常见循环生物标志物的17种特征，并利用纵向收集的数据评估了这些特征与中风、疼痛、腿部溃疡、急性胸综合征、无血管性坏死、癫痫发作、死亡风险以及胎儿血红蛋白和溶血趋势之间的关联。分析表明，一些特征与并发症风险降低相关，而另一些则与并发症风险增加相关。我们还表明，这些特征在另外两项当代镰状细胞病研究中重复出现，并与最近发现的肺血管疾病生物标志物相关。通过重复验证和进一步研究，这些生物标志物特征可能成为一种重要且经济实惠的精准医学工具，有助于疾病的治疗和管理。
