Relevant markers of cancer stem cells indicate a poor prognosis in hepatocellular carcinoma patients: a meta-analysis.

The potential prognostic value of stem cell markers is variably reported, such as CD133 and epithelial cell adhesion molecule. However, their clinical value and significance in hepatocellular carcinoma (HCC) remain controversial. The aim of this study was to carry out a meta-analysis of literature evaluating CD133 and epithelial cell adhesion molecule expression as prognostic factors in HCC and to determine the association between cancer stem cells (CSCs) and common clinical and pathologic features of HCC. The relevant literature was identified using Science Direct, EMBASE, and PubMed. Outcome measures included disease-free survival, overall survival, and relevant pathological parameters. Meta-analyses were carried out using Review Manager, version 5.2. Twelve eligible articles involving 1344 patients were included. Meta-analyses showed that the presence of CSCs was significantly associated with a poor histological grade (OR=3.16, P=0.003) and elevated serum α-fetoprotein level (OR=2.68, P<0.00001). However, there were no significant relations between the presence of CSCs and tumor size, tumor stage, hepatitis, or cirrhosis. The presence of CSCs was significantly associated with poor survival, including overall survival (HR=1.62, P<0.00001) and disease-free survival (HR=1.85, P<0.00001). On the basis of current retrospective evidence, the presence of CSCs is associated with poor histopathologic grade and worse survival in patients with HCC and CD133 plays a significant role in predicting the clinical outcome. Further extensive experimental and clinical research should be carried out to evaluate the role of these markers in clinical practice.