个体化医疗的现状与未来四.生物标志物研究.ppt

个体化医疗的现状与未来四. 生物标志物研究 吕林莉 M.D., Ph.D. 东南大学医学院 Outline 生物标志物的概念 如何评价生物标志物？ 生物标志物的研究方法？ 生物标志物的概念 什么是生物标志物(biomarker)？ “measurable and quantifiable biological parameters” -- a Medical Subject Heading (MeSH) term, 1989 “ A characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes or pharmacological responses to a therapeutic intervention.” --Biomarker Definitions Working Group, 2001,NIH Features of a Useful Biomarker High sensitivity and specificity Easy accessible sample Correlation with histological scoring Change in advance of clinical signs Translational from research to clinical use 不同水平生物标志物 Biomarker Examples Cholesterol is one of the most well-known biomarkers of cardiovascular health Physical measurements: body temperature (fever); blood pressure (stroke risk) Other biomarkers: ? blood sugar level (diabetes) ? antigens (hepatitis) ? proteins (heart attack) ? genetic variations (Huntington’s disease) 生物标志物的临床应用 生物标志物应用现状 目前临床很多疾病的诊断依赖病理诊断，但不能作为常规筛查、监测手段 众多疾病缺乏早期、特异性生物标志物 治疗缺乏个体化方案 Are we treating sub-populations? Novel biomarkers are needed Early, accurate diagnosis -Individualized therapy and improved treatment outcomes Better defined populations will allow more specific drugs -Better efficacy -Fewer side effects Evolution of the biomarkers research High plasma cholesterol and cardiovascular diseases Additional biomarkers (inflammation)Hs-CRP and cardiovascular risk Hs-CRP is the most widely studied biomarker of inflammation in cardiovascular risk. Since the early 1990s with the development of highly sensitive assays for its measurement, correlations of hs-CRP with both cardiovascular risk factors and future cardiovascular events has been possible. CRP and LDL–C levels and the risk of cardiovascular diseases Evolution of the biomarkers research : CRP and LDL-C levels and event-free survival among women 如何评价生物标志物？ 常用评价指标 （一）敏感性 （二）特异性 （三） Youden指数 （四）阳性似然比