Abstract
Cholangiocarcinoma (CCA) is a malignancy arising from cholangiocytes. Currently, the treatment and prognosis for CCA are mostly poor. Recently, we have reported that coiled-coil domain containing 25 (CCDC25) protein level in the sera may be a diagnostic marker for CCA. Subsequently, we identified three binding proteins of CCDC25 and found that kallikrein-11 (KLK11) expression was highest among those binding proteins. In this study, we investigated CCDC25 and KLK11 expression in CCA and adjacent normal tissues (n = 18) using immunohistochemistry. The results demonstrated that the expressions of CCDC25 and KLK11 in CCA tissues were both significantly higher than the adjacent tissues (p < 0.001 and p = 0.001, respectively). Then, using GEPIA bioinformatics analysis, KLK11 mRNA was significantly overexpressed in CCA tumor tissues compared with normal tissues (p < 0.05). Moreover, CCDC25 expression was positively correlated with KLK11 expression in CCA with lymph node metastasis (p = 0.028, r = 0.593). An analysis for the interaction of KLK11 with CCDC25 and other proteins, using STRING version 11.0, revealed that CCDC25 and KLK11 correlated with metastasis-related proteins. In addition, Kaplan-Meier survival curve analysis revealed that a high expression of KLK11 was associated with the poor prognosis of CCA. In conclusion, KLK11 is, as a binding protein for CCDC25, possibly involved in the metastatic process of CCA. KLK11 may be used as a prognostic marker for CCA.
Highlights
Cholangiocarcinoma (CCA) is a malignancy arising from cholangiocytes
coiled-coil domain containing 25 (CCDC25) and KLK11 expression in CCA tissues were examined using immunohistochemistry. For both the CCDC25 and KLK11 stains, the results showed that the normal cholangiocytes monolayer of the intrahepatic bile ducts in the adjacent areas were stained with a light-brown color (Figure 1C,E), whereas the CCA cells were stained with a dark-brown color (Figure 1D,F)
The results show that the expressions of both CCDC25 and KLK11 were significantly higher in cancerous tissues than in the adjacent tissues of CCA with lymph node metastasis (p < 0.001 and p = 0.018, respectively) (Figure 3A,C), but not in the CCA without lymph node metastasis (p = 0.057 and p = 0.057, respectively) (Figure 3B,D)
Summary
Cholangiocarcinoma (CCA) is a malignancy arising from cholangiocytes (bile duct epithelial cells). The disease is highly endemic in Southeast Asia, especially in the Khon Kaen Province, Northeast Thailand [1]. Many factors, such as benign biliary tract disease, primary sclerosing cholangitis, etc., are assumed to be involved in CCA genesis. Opisthorchis viverrini (OV), infection is a common cause of CCA in Northeast Thailand because of the consumption of undercooked fish, the intermediate host of OV, and poor hygiene. Liver fluke infection in association with some carcinogens such as nitrosamine can cause chronic inflammation of cholangiocytes, leading to oxidative DNA damage and subsequent CCA transformation [2]. Nowadays the treatment for CCA is limited and the prognosis of CCA is mostly poor. The majority of CCA cases are unresectable and the recurrence after resection is common [5]
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