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蛋白质组学时代的卵巢癌:诊断、预后及治疗靶点

Ovarian cancer in the proteomics era: diagnosis, prognosis, and therapeutics targets.

作者信息

Boyce E A, Kohn E C

机构信息

Laboratory of Pathology, National Cancer Institute, Bethesda, Maryland 20892, USA.

出版信息

Int J Gynecol Cancer. 2005 Nov-Dec;15 Suppl 3:266-73. doi: 10.1111/j.1525-1438.2005.00434.x.

Abstract

Ovarian cancer is clinically quiet as it plants seeds of metastases in the peritoneal cavity, even during early stages when there is highest potential for cure. The only available biomarker is CA125, which has an unacceptably low sensitivity and specificity for diagnostic use. Highly sensitive and specific tools to further optimize early diagnosis and treatment are needed. We propose that proteomic technologies have an important role to play in the development of these tools. Mass spectrometry platforms, such as surface-enhanced laser desorption/ionization time-of-flight, may be used to mine patient's serum for proteomic signatures that are shed by tumor and stroma. Such signatures could serve as a diagnostic tool during early-stage disease and as a remission-monitoring tool in later-stage disease. Reverse-phase protein microarrays are a new microproteomic tool to profile signaling pathways in ovarian cancer, thus identifying therapeutic targets while simultaneously suggesting prognostic indicators. Proteomic technologies have the capacity to build upon our genomic and clinical understanding of ovarian cancer by moving the focal point to the tumor and its microenvironment. This unique proteomic vantage point allows the creation of tools that will aid clinicians in making rational decisions in the diagnosis and treatment of women with ovarian cancer.

摘要

卵巢癌在临床上较为隐匿,因为即使在早期有最高治愈潜力时,它也会在腹腔内播散转移种子。唯一可用的生物标志物是CA125,其用于诊断时的敏感性和特异性低得令人无法接受。需要高度敏感和特异的工具来进一步优化早期诊断和治疗。我们认为蛋白质组学技术在这些工具的开发中可发挥重要作用。质谱平台,如表面增强激光解吸/电离飞行时间质谱,可用于从患者血清中挖掘由肿瘤和基质释放的蛋白质组特征。这些特征可作为疾病早期的诊断工具以及疾病后期的缓解监测工具。反相蛋白质微阵列是一种新的微蛋白质组学工具,用于描绘卵巢癌中的信号通路,从而识别治疗靶点并同时提示预后指标。蛋白质组学技术有能力在我们对卵巢癌的基因组学和临床认识的基础上,将焦点转移到肿瘤及其微环境。这种独特的蛋白质组学优势视角能够创造出有助于临床医生在卵巢癌女性患者的诊断和治疗中做出合理决策的工具。

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