The effects of the location of cancer stem cell marker CD133 on the prognosis of hepatocellular carcinoma patients

Abstract

BackgroundCD133 (prominin-1) is widely believed to be a cancer stem cell marker in various solid tumor types, and CD133 has been correlated with tumor-initiating capacity. Recently, the nuclear location of CD133 expression in tumors has been discussed, but hepatocellular carcinoma (HCC) has not been included in these discussions. The goal of this study was to investigate the location of CD133 expression in HCC and this location’s potential value as a prognostic indicator of survival in patients with HCC.MethodsWe enrolled 119 cancerous tissues and pair-matched adjacent normal liver tissue from HCC patients. These tissues were obtained immediately after operation, and tissue microarrays were subsequently constructed. The expression of CD133 was measured by immunohistochemistry (IHC), and the correlations between this expression and clinical characteristics and prognosis was estimated using statistical analysis.ResultsThe results showed that the CD133 protein expression levels of HCC in both the cytoplasm and nucleus were significantly higher than adjacent normal liver tissue. Kaplan–Meier survival and Cox regression analyses revealed that high CD133 expression in the cytoplasm was an independent predictor of poor prognosis for the overall survival (OS) and relapse-free survival (RFS) rates of HCC patients (P = 0.028 and P = 0.046, respectively). Surprisingly, high nuclear CD133 expression of HCC was an independent predictor of the good prognosis of the OS and RFS rates of HCC patients (P = 0.023 and P = 0.012, respectively).ConclusionsThe clinical evidence that revealed cytoplasmic CD133 expression was correlated with poor prognosis, while nuclear CD133 expression was significantly correlated with favorable prognosis.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-017-3460-9) contains supplementary material, which is available to authorized users.

Overexpression of Epcam and CD133 Correlates with Poor Prognosis in Dual-phenotype Hepatocellular Carcinoma

“…We found significantly higher levels of EPCAM and CD133 mRNA and protein in DPHCC tissues than in non-DPHCC tissues. Our results are consistent with reports that HCC patients positive for EpCAM or CD133 have poor prognosis, and that EPCAM and CD133 act synergistically in tumors [30][31][32] . EPCAM participates in a Wnt signaling pathway of tumorigenesis 33,34 , while CD133+ cancer cells up-regulate interleukin-8 (IL-8) and activate MAP kinase signaling pathways 35,36 .…”

The role of CD133 in cancer: a concise review

“…Similarly, Ding et al demonstrated that CD133 pos liver cancer cells were resistant to transforming growth factor β (TGF-β)-induced apoptosis and this effect could be blunted using a mitogen-activated protein kinase 1 (MEK1) inhibitor [ 109 ]. Interestingly, a recent study indicated that the location of CD133 on the CSC may play an important role on the aggressiveness of the cancer and the prognosis of the liver cancer patient [ 110 ]. This study analyzed cancerous tissues and pair-matched adjacent normal liver tissues from 119 hepatocellular carcinoma patients and revealed that cytoplasmic CD133 expression was correlated with poor prognosis, while nuclear CD133 expression was correlated with favorable prognosis.…”

Oncogenicity of viral hepatitis B and C in the initiation of hepatic cancer stem cells

“…Multiple clinical studies had shown that the high expression of CSC marker CD133 in HCC tissues, in particular in the cytoplasm, is correlated with a poor prognosis [47][48][49][50][51] . In addition to prognosis, CD90 is highexpressed in HCC nodule [52] and is correlated with HCC differentiation grades [53,54] .…”