CD133 and epithelial cell adhesion molecule expressions in the cholangiocarcinoma component are prognostic factors for combined hepatocellular cholangiocarcinoma

Abstract

Aim A new classification of combined hepatocellular cholangiocarcinoma (CHC) was recently reported. Cancer stem cells have been associated with CHC carcinogenesis. This study examined the association of cancer stem cell marker expression and prognosis in CHC classified using the new classification. Methods We enrolled 26 CHC patients and classified them according to the new classification. We evaluated the expression of cancer stem cell markers (CD56, CD133, and epithelial cell adhesion molecule [EpCAM]) by immunohistochemical staining in each component. We analyzed the association between expressions and prognosis. Results Seven cases were hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA) (cHCC‐CCA), 12 were HCC and intermediate cell carcinoma (HCC‐INT), and seven were intermediate cell carcinoma (INT). The CD133‐positive rate tended to be higher in the CCA (42.9%) and INT component (50.0%) than the HCC component (14.3%) in cHCC‐CCA. In HCC‐INT, the CD133‐positive rate in the INT component (83.3%) was significantly higher than the HCC component (8.3%; P = 0.001). For EpCAM, the positive rate in the CCA component (71.4%) and INT component (50.0%) tended to be higher than the HCC component (14.3%) in cHCC‐CCA. Overall survival and disease‐free survival were significantly worse in cases with CD133‐positive (P = 0.048 and P = 0.048, respectively) or EpCAM‐positive (P = 0.041 and P = 0.041, respectively) CCA component in cHCC‐CCA. Conclusions INT and CCA components showed higher expression rates of cancer stem cell markers than the HCC component. CD133 or EpCAM expression in the CCA component was associated with poor prognosis in cHCC‐CCA.

Identification of a Subtype of Hepatocellular Carcinoma with Poor Prognosis Based on Expression of Genes within the Glucose Metabolic Pathway

“…By comparing the gene expression profiling between the two subtypes, we found that the aggressive Cluster2 tumors had significantly upregulated expression of stemness-related genes such as CA9, EpCAM, MMP9, KRT19, CD24, and PROM1 (CD133). These are well-known markers of stemness traits and are associated with poorer prognostic outcomes in HCC [18,[59][60][61][62]. Based on integrative analysis of genomic and epigenomic data in liver cancer, Woo et al also identified one aggressive cluster of the HCC subtype (iCl1) with the previously mentioned stemness-related genes being on top of the upregulated genes [17], which is similar to our finding.…”

m6A demethylase ALKBH5 maintains stemness of intrahepatic cholangiocarcinoma by sustaining BUB1B expression and cell proliferation

“…S1A-B). Numerous studies suggest that CD133, CD24, CD44, EpCAM, Sox2, and CD49f are biomarkers for the identification of cancer stem-like cells (CSCs) in cholangiocarcinoma [31] , [32] , [33] , [34] , [35] , [36] . To examine the CSC marker expression levels in CSCs after altering ALKBH5 expression, RT-qPCR was conducted to detect RNA expression.…”

INTS8 Predicts a Therapeutic Target for Intrahepatic Cholangiocarcinoma via Integration of Bioinformation Analysis and Experimental Validation

“…Although microsatellite instability relatively frequently occurred in in intraductal papillary neoplasms of the biliary tract, the methylation of hMLH1 was not detected [49] . EpCAM, a stemness-related marker, is positively with the aggressive prognosis in ICC and HCC [50][51] . However, we didn't observe an association between INTS8 and EpCAM in ICC.…”