CD133 Overexpression Correlates with Clinicopathological Features of Gastric Cancer Patients and Its Impact on Survival: a Systematic Review and Meta-analysis

Background: CD133 is one of the most commonly used markers of cancer stem cells (CSCs), which are characterized by their ability for self-renewal and tumorigenicity. However, the clinical and prognostic significance of CD133 in gastric cancer remains controversial. To clarify a precise determinant of the clinical significance of CD133, we conducted a systematic review and meta-analysis to elucidate the correlation of CD133 overexpression with prognosis and clinicopathological features of GC patients.

Methods: A search in the Cochrane Library, PubMed, Medline, Web of Knowledge and Chinese CNKI, CBM (up to Jun 30, 2015) was performed using the following keywords gastric cancer, CD133, AC133, prominin-1, etc. Electronic searches were supplemented by hand searching reference lists, abstracts and proceedings from meetings. Outcomes included overall survival and various clinicopathological features. Two reviewers independently screened the literature according to the inclusion and exclusion criteria, extracted the data, and assessed the methodological quality of the included studies, and then RevMan 5.2.0 software was used for meta-analysis.

Results: A total of 603 gastric cancer patients from 8 studies were included. The results of the meta-analyses showed that, there were significant differences of CD133 expression in the following comparisons: gastric cancer tissues vs. normal esophageal tissue (OR = 3.49, 95% CI [2.48, 490], P < 0.00001), lymph node metastasis vs. non-lymph node metastasis (OR = 2.75, 95% CI [1.99, 3.81], P < 0.00001), distant metastasis vs. non-distant metastasis (OR = 2.38, 95%CI [1.47, 3.85], P < 0.0004), clinical stages III~IV vs. clinical stages I~II (OR = 2.83, 95% CI [2.13, 3.76], P < 0.00001), as well as the accumulative 5-year overall survival rates of CD133-positive vs. CD133-negative patients (OR = 0.23, 95% CI [0.16, 0.33], P < 0.00001).

Conclusion: Overexpression of CD133 is associated with lymph node metastasis, distant metastasis, poor TNM stage. Additionally, CD133-positive gastric cancer patients had worse prognosis. Our results indicate that CD133 may be involved in the carcinogenesis of gastric cancer. Evaluation of cytoplasmic CD133 overexpression in gastric cancer tissue sections may be useful in the future as a novel prognostic factor. Nevertheless, due to the poor quality and small sample size of included trials, more well-designed multi-center randomized controlled trials should be performed.