Clinical significance of stem cell marker CD133 expression in colorectal cancer

Objective: CD133, a glycoprotein, is expressed in different types of human stem cells and tumor cells. Detection of altered CD133 expression in colorectal cancer tissues could be useful as a marker for the prediction of colorectal tumorigenesis, progression, and prognosis. Methods: A total of 19 fresh and 145 paraffin-embedded tissue specimens from colorectal cancer patients were obtained for detection of CD133 expression using flow cytometry and immunohistochemistry, respectively. The tumorigenic capacity of tumor cells from 19 patients was assessed in nude mice. Association of CD133 expression was then analyzed for clinical significance. Results: The percentage of CD133(-) positive (CD133(+)) tumor cell population ranged between 0.84% and 16.75% (mean ratio=7.15%) of tumor cells in the 19 freshly isolated tissue samples. CD133 expression in tumor cells was associated with tumor lymph node metastasis (9.81% vs. 3.22%; p=0.013) and poor tumor differentiation (8.32% vs. 5.07%; p=0.043). In the 145 paraffin-embedded samples, CD133(+) colorectal cancer was also associated with local recurrence of tumorigenesis (p=0.035) and distant metastasis (p=0.017), while patients with over 5% CD133(+) tumor cells exhibited a decreased survival rate (p=0.001). Multivariate COX analysis showed that the depth of tumor invasion, histology, stages, lymph node metastasis, and CD133 expression were all independent prognosis factors for colorectal cancer (p=0.032, 0.011, 0.001, 0.002, and 0.030, respectively). Furthermore, as few as 5,000 CD133(+) colorectal cancer HCT116 cells were sufficient to form tumor xenografts, whereas 1x10(5) CD133(-) tumor cells failed to develop tumor xenografts in nude mice. Conclusions: CD133 expression is a useful biomarker for prediction of colorectal cancer progression and survival of patients.