Downregulation of MAGI1 Associates with Poor Prognosis of Hepatocellular Carcinoma
Downregulation of MAGI1 Associates with Poor Prognosis of Hepatocellular Carcinoma
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DOI：
10.3109/08941939.2011.606875
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发表时间：
2012-04-01
影响因子：
1.9
通讯作者：
Wang, Zhiming
中科院分区：
文献类型：
--
作者：
Zhang, Gewen;Liu, Ting;Wang, Zhiming
目的：MAGI 1（membrane-associated guanylate kinase，WW and PDZ domain containing 1）在粘附连接的稳定和侵袭转移的抑制中起重要作用。然而，其在肝细胞癌（HCC）中的表达及其临床意义尚不清楚。本研究旨在探讨MAGI 1在人肝癌组织中的表达及其临床意义。研究方法：应用逆转录-聚合酶链反应（RT-PCR）和蛋白质印迹法检测31例肝癌和癌旁肝组织（PCLT）中mRNA和蛋白质的表达水平。此外，104例HCC患者的标本进行了MAGI 1表达的化学检测，并分析了MAGI 1水平与预后的相关性。结果：MAGI 1在HCC中的表达水平显著低于PCLT（p <0.01）。重要的是，MAGI 1表达减少与多发性肿瘤结节相关，（p < .05），无包膜形成（p < .05），Edmondson-Steiner分级更差（p < .05），静脉侵犯（p <0.01），缩短中位总生存时间（25个月对42个月; p = 0.013），以及HCC的无病生存时间（20个月对40个月; p = 0.018）。多变量考克斯回归分析显示MAGI 1表达水平是预后的独立因素（p = 0.038）。结论：MAGI 1在HCC中表达降低，与预后不良相关，提示MAGI 1可作为HCC的一种新的预后标志物。
Objective: MAGI1 (membrane-associated guanylate kinase, WW and PDZ domain containing 1) plays an important role in stabilization of adherens junctions and suppression of invasiveness and metastasis. However, its expression and clinical revelance in hepatocellular carcinoma (HCC) are still unknown. So, this study was performed to detect the expression and clinical significance of MAGI1 in human HCC. Methods: The mRNA and protein expression levels were examined by using reverse transcription-PCR (RT-PCR) and Western blotting in 31 paired HCC and paracarcinomatous liver tissues (PCLT). Furthermore, samples of 104 HCC patients were determined immunohistochemically for MAGI1 expression and the correlation of MAGI1 levels with prognosis was analyzed. Results: The expression levels of MAGI1 were significantly downregulated in HCCs than those in PCLTs (p < .01). Importantly, the decreased expression of MAGI1 correlated with multiple tumor nodules (p < .05), absence of capsular formation (p < .05), worse Edmondson-Steiner grade (p < .05), vein invasion (p < .01), shortened median overall survival time (25 versus 42 months; p = .013), and disease-free survival time (20 versus 40 months; p = .018) of HCC. Multivariable Cox regression analysis revealed that MAGI1 expression level was an independent factor for prognosis (p = .038). Conclusions: MAGI1 expression is decreased in HCC, which correlates with poor prognosis, suggesting MAGI1 as a novel prognostic marker for HCC.