美国FDA批准新肿瘤标志物-10-25-09.ppt

美国FDA批准新肿瘤标志物 许洋 中国医学科学院检验医学研发中心 PHENOMICS DISCOVERY PLATFORM 蛋白指纹图谱 蛋白指纹图谱仪10年 1999-2009年 蛋白质组学研究与应用 基因组学研究 ID与定性 分离纯化 临床检验 Petricoin EF, Ardekani AM, Hitt BA, Levine PJ, Fusaro VA, Steinberg SM, Mills GB, Simone C, Fishman DA, Kohn EC, Liotta LA. Food and Drug Administration/National Institutes of Health Clinical Proteomics Program, Department of Therapeutic Proteins/Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD, USA. petricoin@ BACKGROUND: New technologies for the detection of early-stage ovarian cancer are urgently needed. Pathological changes within an organ might be reflected in proteomic patterns in serum. We developed a bioinformatics tool and used it to identify proteomic patterns in serum that distinguish neoplastic from non-neoplastic disease within the ovary. METHODS: Proteomic spectra were generated by mass spectroscopy (surface-enhanced laser desorption and ionisation). A preliminary training set of spectra derived from analysis of serum from 50 unaffected women and 50 patients with ovarian cancer were analysed by an iterative searching algorithm that identified a proteomic pattern that completely discriminated cancer from non-cancer. The discovered pattern was then used to classify an independent set of 116 masked serum samples: 50 from women with ovarian cancer, and 66 from unaffected women or those with non-malignant disorders. FINDINGS: The algorithm identified a cluster pattern that, in the training set, completely segregated cancer from non-cancer. The discriminatory pattern correctly identified all 50 ovarian cancer cases in the masked set, including all 18 stage I cases. Of the 66 cases of non-malignant disease, 63 were recognised as not cancer. This result yielded a sensitivity of 100% (95% CI 93--100), specificity of 95% (87--99), and positive predictive value of 94% (84--99). INTERPRETATION: These findings justify a prospective population-based assessment of proteomic pattern technology as