Association of the Actin-Binding Protein Transgelin with Lymph Node Metastasis in Human Colorectal Cancer
Association of the Actin-Binding Protein Transgelin with Lymph Node Metastasis in Human Colorectal Cancer
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DOI：
10.1593/neo.09542
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发表时间：
2009-09-01
期刊：
影响因子：
4.8
通讯作者：
Dynan, William S.
中科院分区：
文献类型：
--
作者：
Lin, Ying;Buckhaults, Phillip J.;Dynan, William S.
原发性肿瘤的转移性播散导致90%的结直肠癌（CRC）死亡。阳性淋巴结的存在将I/II期CRC与III期CRC分开，是患者管理中的一个特别关键的因素。在这里，我们描述了定量蛋白质组学调查的结果，以确定节点状态的分子相关性。激光捕获显微切割和二维差异凝胶电泳被用来建立表达谱的980个离散的蛋白质特征在24人CRC标本。蛋白质丰度测定的中位技术变异系数为10%，这提供了检测癌症亚型之间微小差异的能力。Transgelin是一种23 kDa的肌动蛋白结合蛋白，是淋巴结状态的首选候选生物标志物。transgelin预测淋巴结状态的受试者工作特征曲线下面积为0.868（P = 0.002）。使用半定量免疫组织化学分析94个独立的组织微阵列上的CRC标本，也发现淋巴结阳性CRC中中度和高水平transgelin表达的频率显著增加（P = 0.036）。在CRC细胞系中的后续研究证实了transgelin在促进侵袭、存活和抗失巢凋亡中的作用。Transgelin定位于CRC细胞的细胞核，其序列和性质表明其可能参与调节与上皮-间质转化相关的转录程序。
Metastatic dissemination of primary tumors is responsible for 90% of colorectal cancer (CRC) deaths. The presence of positive lymph nodes, which separates stage I/II from stage III CRC, is a particularly key factor in patient management. Here, we describe results of a quantitative proteomic survey to identify molecular correlates of node status. Laser capture microdissection and two-dimensional difference gel electrophoresis were used to establish expression profiles for 980 discrete protein features in 24 human CRC specimens. Protein abundances were determined with a median technical coefficient of variation of 10%, which provided an ability to detect small differences between cancer subtypes. Transgelin, a 23-kDa actin-binding protein, emerged as a top-ranked candidate biomarker of node status. The area under the receiver operating characteristic curve for transgelin in predicting node status was 0.868 (P = .002). Significantly increased frequency of moderate- and high-level transgelin expression in node-positive CRC was also seen using semiquantitative immunohistochemistry to analyze 94 independent CRC specimens on tissue microarrays (P = .036). Follow-up studies in CRC cell lines demonstrated roles for transgelin in promoting invasion, survival, and resistance to anoikis. Transgelin localizes to the nucleus of CRC cells, and its sequence and properties suggest that it may participate in regulation of the transcriptional program associated with the epithelialto-mesenchymal transition.