Prognostic significance of Capn4 overexpression in intrahepatic cholangiocarcinoma.
Prognostic significance of Capn4 overexpression in intrahepatic cholangiocarcinoma.
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Capn4 过表达在肝内胆管癌中的预后意义
DOI：
10.1371/journal.pone.0054619
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Fan J
中科院分区：
文献类型：
--
作者：
Zhang C;Bai DS;Huang XY;Shi GM;Ke AW;Yang LX;Yang XR;Zhou J;Fan J
研究背景钙蛋白酶小亚基1（Capn 4）与肝细胞癌的转移/侵袭密切相关。本研究旨在探讨Capn 4在肝内胆管细胞癌（ICC）中的作用。方法采用实时荧光定量聚合酶链反应（real-time PCR）和免疫印迹法（western blot）检测33例ICC组织中Capn 4的表达。用特异性小干扰RNA（small interfering RNA，siRNA）去除Capn 4后，观察Capn 4在ICC细胞迁移、侵袭和增殖中的作用，并观察其对ICC细胞基质金属蛋白酶2（MMP 2）表达的影响。采用免疫组化法检测140例ICC患者和13例正常肝组织中Capn 4的表达，Kaplan-Meier和考克斯回归分析Capn 4在ICC中的预后作用。结果Capn 4在ICC组织中的表达明显高于癌旁组织。Capn 4下调可抑制HCCC-9810和QBC 939细胞的体外迁移/侵袭能力，并降低MMP 2的表达。Capn 4过表达与ICC的淋巴转移（p = 0.026）和肿瘤淋巴结转移（TNM）分期（p = 0.009）显著相关。 Capn 4低组患者的术后2年和5年总生存率高于Capn 4高组。Capn 4low组的累积复发率远低于Capn 4 high组。多因素分析显示Capn 4过表达是ICC独立的预后指标。结论Capn 4过表达与ICC的转移/侵袭有关，Capn 4过表达可作为ICC的分子治疗靶点。
Background Calpain small subunit 1 (Capn4) has been shown to correlate with the metastasis/invasion of hepatocellular carcinoma. This study aimed to investigate the role of Capn4 in intrahepatic cholangiocarcinoma (ICC). Methods Capn4 expression was measured in 33 ICC tissues by quantitative real-time polymerase chain reaction and western blot. The role of Capn4 in the migration, invasion and proliferation of ICC cells and matrix metalloproteinase 2 (MMP2) expression were assessed after Capn4 depletion by specific small interfering RNA. Capn4 expression was further examined by immunohistochemistry in a tissue microarray consisting of 140 ICC patients and 13 normal liver tissues, and the prognostic role of Capn4 in ICC was evaluated by Kaplan-Meier and Cox regression analyses. Results Capn4 expression was significantly higher in the ICC tissues compared to the peritumor tissues. Capn4 down-regulation impaired the migration/invasion ability of HCCC-9810 and QBC939 cells in vitro and decreased MMP2 expression. Capn4 overexpression significantly correlated with the presence of lymphatic metastasis of ICC (p = 0.026) and the tumor-node-metastasis (TNM) stage (p = 0.009). The postoperative 2- and 5-year overall survivals in patients with Capn4low were higher than those in the Capn4high group. The cumulative recurrence rate in patients with Capn4low was much lower than in the Capn4high group. Multivariate analysis showed that Capn4 overexpression was an independent prognostic marker in ICC. Conclusions Capn4 overexpression was implicated in ICC metastasis/invasion, and Capn4 overexpression may be used as a molecular therapeutic target for ICC.
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SERPINB2保护视网膜母细胞瘤免受钙蛋白酶的保护可增强肿瘤细胞的存活。
影响因子：
11.2
作者：
Tonnetti, Laura;Netzel-Arnett, Sarah;Darnell, Grant A.;Hayes, Tamara;Buzza, Marguerite S.;Anglin, Ian E.;Suhrbier, Andreas;Antalis, Toni M.
通讯作者：
Antalis, Toni M.
影响因子：
5.3
作者：
Arthur, JSC;Elce, JS;Greer, PA
通讯作者：
Greer, PA
影响因子：
4.8
作者：
Rosenberger, G;Gal, A;Kutsche, K
通讯作者：
Kutsche, K
影响因子：
7.7
作者：
Li Y;Ma J;Zhu H;Singh M;Hill D;Greer PA;Arnold JM;Abel ED;Peng T
通讯作者：
Peng T
影响因子：
2.4
作者：
Morise, Zenichi;Sugioka, Atsushi;Takeura, Chinatsu
通讯作者：
Takeura, Chinatsu