CD133 Expression and the Prognosis of Colorectal Cancer: A Systematic Review and Meta-Analysis

Abstract

ObjectiveCD133 has recently been reported as a marker of cancer stem-like cells in colorectal cancer (CRC). However, its predictive value in CRC still remains controversial. In this study, we aimed to evaluate the association between the expression of CD133 and clinicopathological features and the outcome of CRC patients by performing a meta-analysis.MethodsA comprehensive literature search for relevant studies published up to December 2012 was performed using PubMed, MEDLINE and ISI Web of Science. Only articles in which CD133 antigen was detected in situ localisation by immunohistochemical staining were included. This meta-analysis was done using RevMan 4.2 software.ResultsWe found that a total of 15 studies involving 810 CD133-high and 1487 CD133-low patients met the inclusion criteria for the analysis of 5-year overall survival (OS) rate. In a random-effects model, the results showed that CD133-high expression in colorectal cancer was an independent prognostic marker correlating with both OS rate (RR = 0.67, 95%CI 0.54–0.82, P<0.01) and disease free survival (DFS) rate (RR = 0.71, 95%CI 0.52–0.96, P = 0.03). CD133-high expression was also associated with more T3,4 tumor invasion, N positive and vascular invasion cases, corresponding to a risk difference of 1.12 (95%CI 1.01–1.23, P = 0.03), 1.31 (95%CI 1.06–1.63, P = 0.01) and 1.24 (95%CI 1.08–1.41, P<0.01), respectively. However, when types of histology, lymphatic invasion and distant metastasis were considered, CD133 overexpression was not significantly related with these clinicopathological parameters.ConclusionOur meta-analysis results suggest that CD133 is an efficient prognostic factor in CRC. Higher CD133 expression is significantly associated with poorer clinical outcome and some clinicopathological factors such as T category, N category and vascular invasion in CRC patients.

The Prognostic Role of Cancer Stem Cell Markers for Long-term Outcome After Resection of Colonic Liver Metastases

“…Other contradicting results were reported by Yamamoto et al who found CD133 expression in liver metastases to be associated with a better OS after hepatectomy (16) and Kishikawa et al who reported both a better OS and DFS (18). Even though discrepancies exist between the results of the few available studies, the current findings are in accordance with results of the considerably larger available material on the prognostic value of CD133 expression in primary CRC, where a meta-analysis associated this with a worse prognosis as well (15). Since there was no significant discordance between CD-133 expression in the primary colon cancer and the liver metastases in the present material, these findings are most likely associated.…”

“…More knowledge exists on these markers' expression in primary colon cancer and outcome after colon cancer treatment, with CD133 being claimed to be associated with both a worsened OS and DFS after colon cancer treatment (15). CD44 expression is found to predict a worsened OS (13), as is CD24 (14).…”

“…CD24 is a heavily glycosylated cell surface protein, thought to have various functions in proliferation and cell adhesion (12). In colorectal cancer patients, CD44 and CD24 have been associated with decreased OS (13,14), whilst a metaanalysis showed that CD133 is correlated with a worsened OS and DFS (15). Studies regarding the expression of these markers in colonic liver metastases and its influence on survival after hepatectomy are sparse (16)(17)(18).…”

CD133/CD166/Ki-67 Triple Immunouorescence Assessment for Putative Cancer Stem Cells in Colon Carcinoma*

“…ese large discrepancies have been attributed mainly to methodological variations and di erent scoring systems [18,46,47]. It seems that only membranous CD133 overexpression correlates with patient survival times, recurrence-free survival times and chemoresistance [21,48]. However, it was speculated that the shi of CD133 from cytoplasmic to a membranous localization underlies the transition of epithelial cells towards a more invasive phenotype [48].…”

Cancer stem cell markers and their prognostic value

“…Повышенные ее уровни в периферической крови предсказывали рецидив колоректального рака независимо от стадии опухоли и уровней раково-эмбрионального анти-гена и были ассоциированы с костными метастазами в раз-личных солидных опухолях [16]. В ряде систематических обзоров и метаанализов показана меньшая выживаемость пациентов с раком желудка [53], яичников [54], немелко-клеточным раком легкого [55], колоректальным раком [56] при высокой экспрессии СD133 в опухоли.…”