Colon cancer stem cell markers CD44 and CD133 in patients with colorectal cancer and synchronous hepatic metastases

Abstract

CD44 and CD133 mRNA expression as cancer stem cell markers in colorectal cancer were correlated with synchronous hepatic metastases and the clinicopathological factors, including patient survival. The CD44 and CD133 mRNA levels in 36 primary colorectal adenocarcinomas with synchronous hepatic metastasis were analyzed by reverse transcriptase polymerase chain reaction, with normalization relative to glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Immunohistochemical analysis was performed on samples with typical mRNA expression patterns to investigate protein expression. Both CD44 and CD133 gene expressions were highest in hepatic metastasis tissue, followed by colorectal cancer and normal mucosa. The differences were statistically significant among groups of normal mucosa, colorectal cancer and hepatic metastasis tissue. CD44 mRNA expression was significantly associated with the tumor location (P=0.019) and histology (P=0.026). With a median follow-up period of 38 months, the 5-year disease-free survival rate of the patients with high CD44 mRNA expression in the CD44 hepatic metastasis tissue group was significantly lower than that of the patients with low expression (P=0.002). While the mRNA expressions in groups of CD44 colorectal tumor, CD133 colorectal tumor, and CD133 hepatic metastasis tissue were not significant. CD44 and CD133 mRNA were highly correlatively co-expressed in colorectal cancer with hepatic metastases. CD44 expression was an independent factor associated with patient survival, while CD133 did not show this pattern. Thus, CD44 is a more reliable marker for predicting hepatic metastases and survival. Larger prospective studies are required to confirm these findings.