Hudson Michael E, Pozdnyakova Irina, Haines Kenneth, Mor Gil, Snyder Michael
Department of Molecular, Cellular, and Developmental Biology, Yale University, 210 Prospect Street, New Haven, CT 06520-8103, USA.
Proc Natl Acad Sci U S A. 2007 Oct 30;104(44):17494-9. doi: 10.1073/pnas.0708572104. Epub 2007 Oct 22.
Ovarian cancer is a leading cause of deaths, yet many aspects of the biology of the disease and a routine means of its detection are lacking. We have used protein microarrays and autoantibodies from cancer patients to identify proteins that are aberrantly expressed in ovarian tissue. Sera from 30 cancer patients and 30 healthy individuals were used to probe microarrays containing 5,005 human proteins. Ninety-four antigens were identified that exhibited enhanced reactivity from sera in cancer patients relative to control sera. The differential reactivity of four antigens was tested by using immunoblot analysis and tissue microarrays. Lamin A/C, SSRP1, and RALBP1 were found to exhibit increased expression in the cancer tissue relative to controls. The combined signals from multiple antigens proved to be a robust test to identify cancerous ovarian tissue. These antigens were also reactive with tissue from other types of cancer and thus are not specific to ovarian cancer. Overall our studies identified candidate tissue marker proteins for ovarian cancer and demonstrate that protein microarrays provide a powerful approach to identify proteins aberrantly expressed in disease states.
卵巢癌是导致死亡的主要原因之一,但该疾病生物学的许多方面以及常规检测手段仍很缺乏。我们利用蛋白质微阵列和癌症患者的自身抗体来鉴定在卵巢组织中异常表达的蛋白质。使用30名癌症患者和30名健康个体的血清来探测包含5005种人类蛋白质的微阵列。鉴定出94种抗原,相对于对照血清,癌症患者血清中这些抗原表现出增强的反应性。通过免疫印迹分析和组织微阵列对四种抗原的差异反应性进行了检测。相对于对照,发现核纤层蛋白A/C、SSRP1和RALBP1在癌组织中表达增加。来自多种抗原的组合信号被证明是识别癌性卵巢组织的有力检测方法。这些抗原也与其他类型癌症的组织发生反应,因此并非卵巢癌所特有。总体而言,我们的研究鉴定出了卵巢癌的候选组织标记蛋白,并证明蛋白质微阵列提供了一种强大的方法来鉴定在疾病状态下异常表达的蛋白质。