CD133 expression in cancer cells predicts poor prognosis of non-mucin producing intrahepatic cholangiocarcinoma

Abstract

Abstract Background CD133 is a marker of stem cells as well cancer stem cells. This study investigated the association between CD133 expression in cancer cells and the clinical outcome of non-mucin producing intrahepatic cholangiocarcinoma (ICC). Methods Fifty-seven non-mucin producing ICC patients were enrolled in this study. Immunohistochemistry (IHC) and immunofluorescence staining for CD133 as well as other cancer-associated proteins, including cytokeratin 19, TGF-β1, p-Smad2 and epithelial–mesenchymal transition (EMT) markers S100A4, E-Cadherin and Vimentin were analyzed. Results IHC staining showed that tumor cells in 52.6% of patients expressed CD133. The CD133+ patients had significantly higher metastasis rate than those without CD133+ tumor cells (36.7% vs. 10.1%, p = 0.03). The CD133+ patients had shorter overall and disease-free survival time as compared to the CD133− patients. Furthermore, 90.9% of CD133+ patients developed cancer recurrence, as compared to 64.3% of CD133− patients (p = 0.02). As compared to CD133− patients, tumor cells in CD133+ patients demonstrated high levels of TGF-β/p-Smad2 as well as EMT-like alteration, characterized by loss of E-Cadherin and expression of Vimentin and S100A4. Conclusions CD133 expression in ICC tumor cells indicates poor prognosis of the disease and might be associated with TGF-β related EMT alterations.

Keywords

• Intrahepatic cholangiocarcinoma
• CD133
• Epithelial–mesenchymal transition