Characterization of Molecular Markers Indicative of Cervical Cancer Progression.
Characterization of Molecular Markers Indicative of Cervical Cancer Progression.
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DOI：
10.1002/prca.200800068
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发表时间：
2009-05-05
影响因子：
2
通讯作者：
Dynan, William S.
中科院分区：
文献类型：
--
作者：
Arnouk, Hilal;Merkley, Mark A.;Podolsky, Robert H.;Stoeppler, Hubert;Santos, Carlos;Alvarez, Manuel;Mariategui, Julio;Ferris, Daron;Lee, Jeffrey R.;Dynan, William S.
关键词：
宫颈癌起源于人乳头瘤病毒（HPV）感染，并通过组织学定义的癌前分期进展。在这里，我们比较了来自同一患者群体的正常宫颈上皮和患者匹配的高级别鳞状上皮内病变（HSIL）与宫颈癌组织（每组n=10）。采用激光捕获显微解剖和2D-DIGE相结合的方法对标本进行分析。在53个位点上观察到显著的表达变化，从而在分子水平上鉴定出23个独特的蛋白。其中8个能区分正常上皮和HSIL， 4个能区分HSIL和癌。此外，一种叫做角蛋白的蛋白质区分了这三种状态。其他鉴定的蛋白质包括分化标记物、致癌基因DJ-1、蛇形蛋白、应激和干扰素反应蛋白、解毒酶和血清转运蛋白。对所有已鉴定的蛋白进行的文献回顾表明，大多数变化可归因于以下三种原因之一：直接或间接的HPV癌蛋白相互作用、潜伏期间的生长选择或病变微环境中的相互作用。选择的结果通过免疫组织化学证实，使用来自同一队列的冷冻切片或来自组织微阵列的福尔马林固定石蜡包埋样品。本文描述的新型标记物具有潜在的应用价值，可以提高当前筛选方法的预测价值。
Cervical cancer originates with human papillomavirus (HPV) infection and progresses via histologically-defined premalignant stages. Here we compare normal cervical epithelium and patient-matched high grade squamous intraepithelial lesions (HSIL) with cervical carcinoma tissue from the same patient population (n=10 per group). Specimens were analyzed by combined laser capture microdissection and 2D-DIGE. Significant expression changes were seen with 53 spots resulting in identification of 23 unique proteins at the molecular level. These include eight that uniquely distinguish normal epithelium and HSIL and four that uniquely distinguish HSIL and carcinoma. In addition, one protein, cornulin, distinguishes all three states. Other identified proteins included differentiation markers, oncogene DJ-1, serpins, stress and interferon-responsive proteins, detoxifying enzymes, and serum transporters. A literature review, performed for all identified proteins, allowed most changes to be assigned to one of three causes: direct or indirect HPV oncoprotein interactions, growth selection during latency, or interactions in the lesion microenvironment. Selected findings were confirmed by immunohistochemistry using either frozen sections from the same cohort or formalin fixed paraffin embedded samples from a tissue microarray. Novel markers described here have potential applications for increasing the predictive value of current screening methods.
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