Abstract

10504 Background: CD133 is a specific stem cell marker that enriches cancer stem cells of many tumor types including colon cancer as well as circulating endothelial progenitors (CEP). CEP is vital in postnatal angiogenesis and elevated CEP is a proven favoable prognositic marker for heart disease but a potentially poor prognostic marker for cancer. We examined whether elevated CD133 mRNA expression levels in peripheral blood mononuclear cells (PBMC) predict recurrence in colon cancer patients. Methods: We developed and validated a semi-quantitative real-time RT-PCR to quantify CD133 mRNA levels relative to GADPH mRNA. Sixty-six colon cancer patients were enrolled between February 2002 and December 2003. The protocol excluded patients with history of cardiac disease or surgery < 4 weeks from the enrollment and were followed for recurrence for a median 30 months. A central statistician performed multivariate unconditional logistics regression analysis. Results: Among the patients without recurrence, 93% had a CD133 mRNA level < 4.79, whereas 7% had a CD133 mRNA value ≥ 4.79 (p = 0.029). Among patients with a CD133 mRNA value ≥ 4.79, 85% had experienced recurrence compared to 15% of the patient who had no recurrence (p = 0.03). Elevated CD133 mRNA levels at a cut-off point ≥ 4.79 versus < 4.79 were associated with an odd ratio of 22.6 for recurrence (95% CI, 1.7–291.2; p = 0.02); in comparison, the odds ratio for recurrence was 17.2 (95% CI, 1.8–164; p = 0.01) for stage IV patients versus stage I-III patients. No other predictive variables for recurrence were identified including age, race, sex, tumor differentiation, smoking, and diabetes etc. We also observed an trend of association with elevated carcinoma embryonic antigen (CEA) levels (p = 0.03, one sided) and a decreased survival (p = 0.035, one sided) with elevated CD133 mRNA level at a cutoff point ≥ 4.79. Conclusions: Elevated CD133 mRNA levels at a cutoff ≥ 4.79 in PBMC predict colon cancer recurrence independent of stage IV disease. The current assay has certain advantages over flow cytometry for wider clinical application. CD133+ cells measured by CD133 mRNA may contain both CEP and cancer stem cells, leading to increased risks of recurrence. No significant financial relationships to disclose.

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