Immunotope, Inc., Doylestown, PA, 18902, USA.
J Cancer Res Clin Oncol. 2013 Oct;139(10):1757-70. doi: 10.1007/s00432-013-1501-6. Epub 2013 Sep 3.
CA-125 has been a valuable marker for detecting ovarian cancer, however, it is not sensitive enough to detect early-stage disease and not specific to ovarian cancer. The purpose of our study was to identify autoantibody markers that are specific to ovarian cancer regardless of CA-125 levels.
Top-down and iTRAQ quantitative proteomics methods were used to identify high-frequency autoantibodies in ovarian cancer. Protein microarrays comprising the recombinant autoantigens were screened using serum samples from various stages of ovarian cancer with diverse levels of CA-125 as well as benign and healthy controls. ROC curve and dot blot analyses were performed to validate the sensitivity and specificity of the autoantibody markers.
The proteomics methodologies identified more than 60 potential high-frequency autoantibodies in ovarian cancer. Individual serum samples from ovarian cancer stages I-IV compared to control samples that were screened on a microarray containing native recombinant autoantigens revealed a panel of stage I high-frequency autoantibodies. Preliminary ROC curve and dot blot analyses performed with the ovarian cancer samples showed higher specificity and sensitivity as compared to CA-125. Three autoantibody markers exhibited higher specificity in various stages of ovarian cancer with low and normal CA-125 levels.
Proteomics technologies are suitable for the identification of protein biomarkers and also the identification of autoantibody biomarkers when combined with protein microarray screening. Using native recombinant autoantigen arrays to screen autoantibody markers, it is possible to identify markers with higher sensitivity and specificity than CA-125 that are relevant to early detection of ovarian cancer.
CA-125 一直是检测卵巢癌的有价值的标志物，然而，它的灵敏度不够高，无法检测早期疾病，也不够特异于卵巢癌。我们的研究目的是确定与 CA-125 水平无关的特异性卵巢癌自身抗体标志物。
采用自上而下和 iTRAQ 定量蛋白质组学方法鉴定卵巢癌中的高频自身抗体。使用来自不同 CA-125 水平和良性及健康对照的各种阶段卵巢癌的血清样本筛选包含重组自身抗原的蛋白质微阵列。进行 ROC 曲线和点印迹分析以验证自身抗体标志物的灵敏度和特异性。
蛋白质组学方法鉴定了卵巢癌中超过 60 种潜在的高频自身抗体。与对照样本相比，I-IV 期卵巢癌的个体血清样本在包含天然重组自身抗原的微阵列上进行筛选，揭示了一组 I 期高频自身抗体。使用卵巢癌样本进行的初步 ROC 曲线和点印迹分析显示，与 CA-125 相比，特异性和灵敏度更高。在 CA-125 水平低和正常的各种卵巢癌阶段，有 3 种自身抗体标志物显示出更高的特异性。
蛋白质组学技术适合于鉴定蛋白质生物标志物，当与蛋白质微阵列筛选结合使用时，也适合于鉴定自身抗体生物标志物。使用天然重组自身抗原阵列筛选自身抗体标志物，有可能确定比 CA-125 具有更高灵敏度和特异性的标志物，这些标志物与卵巢癌的早期检测相关。
