Department of Hepatobiliary Surgery, Clinical Medical College of Yangzhou University, Yangzhou, People's Republic of China.
PLoS One. 2013;8(1):e54619. doi: 10.1371/journal.pone.0054619. Epub 2013 Jan 22.
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).
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.
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 Capn4(low) were higher than those in the Capn4(high) group. The cumulative recurrence rate in patients with Capn4(low) was much lower than in the Capn4(high) group. Multivariate analysis showed that Capn4 overexpression was an independent prognostic marker in ICC.
Capn4 overexpression was implicated in ICC metastasis/invasion, and Capn4 overexpression may be used as a molecular therapeutic target for ICC.
钙蛋白酶小亚基 1（Capn4）的表达与肝癌的转移和侵袭相关。本研究旨在探讨 Capn4 在肝内胆管癌（ICC）中的作用。
通过实时定量聚合酶链反应和 Western blot 检测 33 例 ICC 组织中 Capn4 的表达。通过特异性小干扰 RNA 敲低 Capn4 后，评估 Capn4 对 ICC 细胞迁移、侵袭和增殖以及基质金属蛋白酶 2（MMP2）表达的影响。在由 140 例 ICC 患者和 13 例正常肝组织组成的组织微阵列中，通过免疫组织化学进一步检测 Capn4 的表达，并通过 Kaplan-Meier 和 Cox 回归分析评估 Capn4 在 ICC 中的预后作用。
ICC 组织中 Capn4 的表达明显高于肿瘤旁组织。Capn4 下调可削弱 HCCC-9810 和 QBC939 细胞的体外迁移/侵袭能力，并降低 MMP2 的表达。Capn4 的过表达与 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。Capn4（低）表达的患者术后 2 年和 5 年总生存率均高于 Capn4（高）表达的患者。Capn4（低）表达患者的累积复发率明显低于 Capn4（高）表达的患者。多因素分析显示，Capn4 过表达是 ICC 的独立预后标志物。
Capn4 的过表达参与了 ICC 的转移和侵袭，Capn4 过表达可能成为 ICC 的分子治疗靶点。
