Transgelin as a suppressor is associated with poor prognosis in colorectal carcinoma patients
Transgelin as a suppressor is associated with poor prognosis in colorectal carcinoma patients
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Transgelin 作为抑制剂与结直肠癌患者预后不良相关
DOI：
10.1038/modpathol.2009.29
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发表时间：
2009-06-01
期刊：
影响因子：
7.5
通讯作者：
Ding, Yan-Qing
中科院分区：
文献类型：
--
作者：
Zhao, Liang;Wang, Hui;Ding, Yan-Qing
我们对结直肠癌进行了比较蛋白质组学分析，以研究与癌发生和预后相关的潜在靶蛋白。其中，transgelin是一种分子量为22 kDa的蛋白质，也被称为SM 22，被鉴定为一种新的肿瘤抑制蛋白，但迄今为止对该蛋白在肿瘤中的作用知之甚少。transgelin在大肠癌组织中的表达明显低于正常大肠粘膜。5-氮-2 ′-脱氧胞苷作为去甲基化剂，可明显恢复transgelin基因的表达水平，提示transgelin基因的DNA甲基化在大肠癌transgelin基因转录调控中起重要作用。作为对照，在细胞系水平的研究证实transgelin蛋白来自上皮细胞而不是间充质细胞。此外，transgelin的免疫组化染色的石蜡切片62例和126例正常大肠粘膜和大肠癌标本，分别进行。与正常结直肠组织相比，我们观察到transgelin在结直肠癌样品中的表达显著降低（P<0.001）。生存分析表明，无transgelin表达的患者总生存期较短，而transgelin表达的患者生存期较好（P=0.006）。多因素分析显示，transgelin阴性表达是患者生存的独立预后指标。我们的研究结果表明，transgelin作为一个抑制剂可能作为一个重要的生物标志物的恶性肿瘤。transgelin缺失涉及基因启动子高甲基化，并与结直肠癌患者总体生存率低密切相关。
We performed comparative proteomic analysis of colorectal cancer to investigate potential target proteins correlated with carcinogenesis and prognosis. Among them, transgelin, a 22 kDa protein also called SM22, was identified as a novel tumor suppressor protein, but little is known about this protein in tumors so far. A remarkable reduced expression of transgelin was found in colorectal cancer samples compared with normal colorectal mucosa. The effect of 5-aza-2′-deoxycytidine as a demethylation agent would obviously restore the original expression level of transgelin, implicating DNA hypermethylation of transgelin is important in the regulation of transgelin transcription in colorectal cancer. As a control, the investigation at cell line level confirms that transgelin protein comes from epithelium but not mesenchymal cells. Further, immunohistochemical staining for transgelin was performed on paraffin sections of 62 and 126 cases of normal colorectal mucosa and colorectal cancer specimens, respectively. As compared to normal colorectal tissue, we observed a significantly lower transgelin expression in colorectal cancer samples (P<0.001). Survival analysis demonstrated that patients without transgelin expression had shorter overall survival, whereas patients with transgelin expression had better survival (P=0.006). Multivariate analysis showed that negative transgelin expression was an independent prognostic indicator for patient's survival. Our results suggest that transgelin as a suppressor may serve as important biomarker of malignancy. Loss of transgelin involves gene promoter hypermethylation and is closely associated with poor overall survival in colorectal cancer patients.