Prognostic significance of Capn4 overexpression in intrahepatic cholangiocarcinoma.
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 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.


CONCLUSIONS
Capn4 overexpression was implicated in ICC metastasis/invasion, and Capn4 overexpression may be used as a molecular therapeutic target for ICC.
Department of Hepatobiliary Surgery, Clinical Medical College of Yangzhou University, Yangzhou, People's Republic of China.
Chi
C
Zhang
Dou-Sheng
DS
Bai
Xiao-Yong
XY
Huang
Guo-Ming
GM
Shi
Ai-Wu
AW
Ke
Liu-Xiao
LX
Yang
Xin-Rong
XR
Yang
Jian
J
Zhou
Jia
J
Fan
D000328:Adult; D000368:Aged; D001650:Bile Duct Neoplasms; D001653:Bile Ducts, Intrahepatic; D002154:Calpain / Q000235:genetics*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018281:Cholangiocarcinoma / Q000235:genetics* / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology; D008207:Lymphatic Metastasis / Q000235:genetics / Q000473:pathology; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D011379:Prognosis; D016016:Proportional Hazards Models
D002154:Calpain; C527669:CAPNS1 protein, human; D020778:Matrix Metalloproteinase 2