Expression of CD133 cancer stem cell marker in melanoma: a systematic review and meta-analysis

Abstract CD133-positive melanoma cells are thought to be melanoma-initiating cells with cancer stem cell (CSC) characteristics. Some researchers have reported that CD133-negative subsets can also initiate tumors, so the clinical significance of a CD133-positive subpopulation of cells in melanoma remains controversial. This systematic review was designed to assess the value of CD133 as a CSC marker in melanomas. A meta-analysis was also performed to cumulatively analyze the data on CD133 expression levels in the selected studies. Eligible studies were identified via an electronic search through various databases including PubMed, MEDLINE, Ovid MEDLINE, and Web of Science (from May 2005 through September 2014) using the following keywords: "CD133 or prominin-1", "cancer stem cells", and "melanoma". Only articles in which CD133 antigen was detected by immunohistochemistry (IHC) were included. A meta-analysis was performed to identify any association between CD133 expression and clinical outcomes. Two hundred and ninety-nine melanoma cases from 5 studies were evaluated for expression levels of CD133 using IHC. Large heterogeneity was observed among the results (p<0.001, I2 = 94%). Approximately 47.9% (95% CI 23.7%-72.1%) of the studied melanoma cases had high CD133 expression. The I2 value and Q-test p value for heterogeneity were 89.0% and <0.001, respectively, and the pooled estimate of CD133 expression was 61.7% (95% CI 25.1%-98.4%). Our findings suggest that CD133 is not yet proven to be an appropriate biomarker in identifying CSCs of melanoma. Thus, detection of CD133 in combination with other putative CSC markers may be more valuable for clinical application.