Is CD133 Expression a Prognostic Biomarker of Non-Small-Cell Lung Cancer? A Systematic Review and Meta-Analysis

<div><p>Background</p><p>The clinical and prognostic significance of CD133 in non-small-cell lung cancer (NSCLC) remains controversial. To clarify a precise determinant of the clinical significance of CD133, we conducted a systematic review and meta-analysis to evaluate the association of CD133 with prognosis and clinicopathological features of NSCLC patients.</p><p>Methods</p><p>The electronic and manual searches were performed through the database of Pubmed, Medline, Web of Science, Scopus, and Chinese CNKI (from January 1, 1982 to January 1, 2014) for titles and abstracts by using the following keywords: “CD133”, “ac133” or “Prominin-1”, and “lung cancer” to identify the studies eligible for our analysis. Meta-analysis was performed by using Review Manager 5.0 and the outcomes included the overall survival and various clinicopathological features.</p><p>Results</p><p>A total of 23 studies were finally included, and our results showed that CD133 level was significantly correlated with the overall survival (OR = 2.25, 95% CI: 1.24–4.07, <i>P</i> = 0.008) of NSCLC patients but not with the disease free survival (OR = 1.33, 95% CI = 0.77–2.30, <i>P</i> = 0.31). With respect to clinicopathological features, CD133 level was positively correlated with lymph node metastasis (OR = 1.99, 95%CI = 1.06–3.74, <i>P</i> = 0.03), but not correlated with the histological classification (OR = 1.00, 95%CI = 0.81–1.23, <i>P</i> = 0.99(ac), OR = 0.87, 95%CI = 0.61–1.24, <i>P</i> = 0.45(sc)), or differentiation (OR = 0.94, 95%CI 0.53–1.68, Z = 0.20, <i>P</i> = 0.84 random-effect) of NSCLC patients.</p><p>Conclusion</p><p>High level of CD133 expression trends to correlate with a worse prognosis and a higher rate of lymph node metastasis in NSCLC patients, revealing CD133 as a potential pathological prognostic marker for NSCLC patients.</p></div

Meta-analysis of correlation between CD133 expression and lymph node metastasis in NSCLC patients.

<p>Meta-analysis of correlation between CD133 expression and lymph node metastasis in NSCLC patients.</p

Meta-analysis of disease free survival between CD133 positive and CD133 negative in NSCLC patients.

<p>Meta-analysis of disease free survival between CD133 positive and CD133 negative in NSCLC patients.</p

Meta-analysis of overall survival between CD133 positive and CD133 negative in NSCLC patients.

<p>Meta-analysis of overall survival between CD133 positive and CD133 negative in NSCLC patients.</p

Flow chart for selection of studies.

<p>Flow chart for selection of studies.</p

Forrest plot of odds ratios for the association of CD133 expression with adenocarcinoma in NSCLC patients.

<p>Forrest plot of odds ratios for the association of CD133 expression with adenocarcinoma in NSCLC patients.</p

Meta-analysis of correlation between CD133 expression and differentiation in NSCLC patients.

<p>Meta-analysis of correlation between CD133 expression and differentiation in NSCLC patients.</p

General characteristics of included studies.

<p>General characteristics of included studies.</p

Narrative review of the association between clinicopathological parameters and CD133 positive expression with respect to non-small-cell-lung cancer patients.

<p>Narrative review of the association between clinicopathological parameters and CD133 positive expression with respect to non-small-cell-lung cancer patients.</p

Examination of POU5F1 and MMP-2 by immunostaining and Western blot analyses.

<p>(<b>A</b>) Immunostaining of POU5F1 and MMP-2 observed by confocal scanning microscopy. (<b>B</b>) Expression of stem cell transcription factor POU5F1 was detected by Western blot. (<b>C</b>) Immunohistochemical analysis of MMP-2 protein in tumor tissues formed by A549 LACSLCs and monolayer cells. Representative images of MMP-2 expression by IHC staining (20×) (<i>left panel</i>). Quantitative analysis of MMP-2 protein levels in tumor tissues formed by A549 LACSLCs and monolayer cells. All experiments were carried out at least in triplicates and the data are presented as the mean ± SEM. Student <i>t</i> test was performed to evaluate the difference.</p