Abstract
Various CD44 isoforms are expressed in several cancer stem cells during tumor progression and metastasis. In particular, CD44 variant 9 (CD44v9) is highly expressed in chronic inflammation-induced cancer. We investigated the expression of CD44v9 and assessed whether CD44v9 is a selective biomarker of human cholangiocarcinoma (CCA). The expression profile of CD44v9 was evaluated in human liver fluke Opisthorchis viverrini-related CCA (OV-CCA) tissues, human CCA (independent of OV infection, non-OV-CCA) tissues, and normal liver tissues. CD44v9 overexpression was detected by immunohistochemistry (IHC) in CCA tissues. There was a higher level of CD44v9 expression and IHC score in OV-CCA tissues than in non-OV-CCA tissues, and there was no CD44v9 staining in the bile duct cells of normal liver tissues. In addition, we observed significantly higher expression of inflammation-related markers, such as S100P and COX-2, in OV-CCA tissues compared to that in non-OV and normal liver tissues. Thus, these findings suggest that CD44v9 may be a novel candidate CCA stem cell marker and may be related to inflammation-associated cancer development.
Highlights
Infection and chronic inflammation are important factors for carcinogenesis, and cholangiocarcinoma (CCA) is a specific type of inflammation-associated cancer
There was no significant difference in age distribution between non-Opisthorchis viverrini (OV) and Opisthorchis viverrini-related CCA (OV-CCA) groups
The level of CD44 variant 9 (CD44v9) expression was significantly higher in cancer cells of CCA patients, in OV-CCA, than in normal liver tissues
Summary
Infection and chronic inflammation are important factors for carcinogenesis, and cholangiocarcinoma (CCA) is a specific type of inflammation-associated cancer. Potential risk factors of CCA are parasitic infections (Opisthorchis viverrini and Clonorchis sinensis), bile duct disorders (biliary tract cysts and hepatolithiasis), toxins, complications (diabetes, cirrhosis, and obesity), alcohol consumption, and smoking [1]. The incidence of CCA has risen globally, and the highest rate occurs in Thailand, in northeastern regions such as Khon Kaen. In Khon Kaen Province, high prevalence of CCA cases is related to Opisthorchis viverrini (OV) infection [2]. The diagnosis of CCA is difficult because of clinical silence and a nonspecific appearance. Discovering specific molecular biomarkers may aid early and definitive diagnosis of CCA
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