Abstract
BackgroundCalpain 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).MethodsCapn4 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.ResultsCapn4 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.ConclusionsCapn4 overexpression was implicated in ICC metastasis/invasion, and Capn4 overexpression may be used as a molecular therapeutic target for ICC.
Highlights
Intrahepatic cholangiocarcinoma (ICC), a primary malignant liver neoplasm secondary to hepatocellular carcinoma (HCC), arises from the intrahepatic biliary epithelia lining the epithelia and peribiliary glands [1]
To assess the role of Capn4 in intrahepatic cholangiocarcinoma (ICC) cells in vitro, we knocked down Capn4 expression in HCCC-9810 cells by RNA interference
Western blot analysis revealed that matrix metalloproteinase 2 (MMP2) expression decreased when Capn4 was downregulated in HCCC-9810 and QBC939 cells (Fig. 1E)
Summary
Intrahepatic cholangiocarcinoma (ICC), a primary malignant liver neoplasm secondary to hepatocellular carcinoma (HCC), arises from the intrahepatic biliary epithelia lining the epithelia and peribiliary glands [1]. Surgical resection of the involved liver segments is the only curative treatment for this devastating disease. The resectability rate has been quite low and variable (18–70%) because most patients present at an advanced stage [3]. The majority of ICC patients have a poor prognosis, even after surgical resection. An improved understanding of the molecular mechanisms associated with ICC progression is needed and would be beneficial in developing effective therapeutic strategies. 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 Capn in intrahepatic cholangiocarcinoma (ICC)
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