Jacobs Ian J, Menon Usha
Department of Gynaecological Oncology, Cancer Institute, Bart's and The London, Queen Mary's School of Medicine & Dentistry, London EC1M 6GR, United Kingdom.
Mol Cell Proteomics. 2004 Apr;3(4):355-66. doi: 10.1074/mcp.R400006-MCP200. Epub 2004 Feb 5.
Ovarian cancer is characterize by few early symptoms, presentation at an advanced stage, and poor survival. As a result, it is the most frequent cause of death from gynecological cancer. During the last decade, a research effort has been directed toward improving outcomes for ovarian cancer by screening for preclinical, early stage disease using both imaging techniques and serum markers. Numerous biomarkers have shown potential in samples from clinically diagnosed ovarian cancer patients, but few have been thoroughly assessed in preclinical disease and screening. The most thoroughly investigated biomarker in ovarian cancer screening is CA125. Prospective studies have demonstrated that both CA125 and transvaginal ultrasound can detect a significant proportion of preclinical ovarian cancers, and refinements in interpretation of results have improved sensitivity and reduced the false-positive rate of screening. There is preliminary evidence that screening can improve survival, but the impact of screening on mortality from ovarian cancer is still unclear. Prospective studies of screening are in progress in both the general population and high-risk population, including the United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS), a randomized trial involving 200,000 postmenopausal women designed to document the impact of screening on mortality. Recent advances in technology for the study of the serum proteome offer exciting opportunities for the identification of novel biomarkers or patterns of markers that will have greater sensitivity and lead time for preclinical disease than CA125. Considerable interest and controversy has been generated by initial results utilizing surface-enhanced laser desorption/ionization (SELDI) in ovarian cancer. There are challenging issues related to the design of studies to evaluate SELDI and other proteomic technology, as well as the reproducibility, sensitivity, and specificity of this new technology. Large serum banks such as that assembled in UKCTOCS, which contain preclinical samples from patients who later developed ovarian cancer and other disorders, provide a unique resource for carefully designed studies of proteomic technology. There is a sound basis for optimism that further developments in serum proteomic analysis will provide powerful methods for screening in ovarian cancer and many other diseases.
卵巢癌的特点是早期症状较少、多在晚期出现且生存率低。因此，它是妇科癌症最常见的死因。在过去十年中，研究工作一直致力于通过使用成像技术和血清标志物筛查临床前的早期疾病，以改善卵巢癌的治疗效果。许多生物标志物在临床诊断的卵巢癌患者样本中显示出潜力，但在临床前疾病和筛查中进行全面评估的却很少。在卵巢癌筛查中研究最深入的生物标志物是CA125。前瞻性研究表明，CA125和经阴道超声都能检测出相当比例的临床前卵巢癌，对结果解释的改进提高了敏感性并降低了筛查的假阳性率。有初步证据表明筛查可提高生存率，但筛查对卵巢癌死亡率的影响仍不明确。在普通人群和高危人群中都在进行筛查的前瞻性研究，包括英国卵巢癌筛查协作试验（UKCTOCS），这是一项涉及20万名绝经后妇女的随机试验，旨在记录筛查对死亡率的影响。血清蛋白质组研究技术的最新进展为鉴定新型生物标志物或标志物模式提供了令人兴奋的机会，这些新型生物标志物或标志物模式对临床前疾病的敏感性和领先时间将比CA125更高。利用表面增强激光解吸/电离（SELDI）技术在卵巢癌研究中取得的初步结果引发了相当大的关注和争议。在评估SELDI和其他蛋白质组学技术的研究设计以及这项新技术的可重复性、敏感性和特异性方面存在具有挑战性的问题。像UKCTOCS中收集的大型血清库，其中包含后来患卵巢癌和其他疾病患者的临床前样本，为精心设计的蛋白质组学技术研究提供了独特的资源。有充分的理由乐观地认为，血清蛋白质组分析的进一步发展将为卵巢癌和许多其他疾病的筛查提供有力方法。
