Elevated circulating endothelial progenitor marker CD133 messenger RNA levels predict colon cancer recurrence

BACKGROUND. CD133 is a specific surface marker for bone marrow-derived circulating endothelial progenitors, which are vital in postnatal physiologic and pathologic (eg, tumor) angiogenesis. In this study, the authors examined whether increased levels of expression of CD133 messenger RNA (mRNA) in peripheral blood predicted disease recurrence in patients with colon cancer. METHODS. Semiquantitative real-time reverse transcriptase-polymerase chain reaction analysis was used to quantify CD133 mRNA levels in peripheral blood mononuclear cells from patients with colon cancer. The assay was developed first and tested at laboratory A (n = 34) and then was validated independently at laboratory B (n = 66). All patients were enrolled between February 2002 and December 2003. A central statistician performed the analysis. RESULTS. At laboratory A, the median CD133 mRNA level was elevated in patients with recurrent disease (4.2; range, 0.017-106.9) compared with patients without recurrence (0.0017; range, 0.0-9.51; P <.001), leading to a 14.6 odds ratio of recurrence (95% confidence interval [95% CI], 1.7-126; P = .004). At laboratory B, it was confirmed that elevated CD133 mRNA levels at a cutoff point ≥4.79 versus <4.79 were associated with an odds ratio of 22.6 for recurrence (95% CI, 1.7-291.2; P =.02). By comparison, the odds ratio for recurrence was 17.2 (95% CI, 1.8-164; P = .01) for patients with stage III-IV disease versus stage I-II disease according to the Tumor, Lymph Node, Metastasis (TNM) classification. An association also was observed between elevated carcinoma embryonic antigen levels (P =.03; 1-sided) and decreased survival (P =.035; 1-sided) with a CD133 mRNA cutoff level of ≥4.79. CONCLUSIONS. Elevated CD133 mRNA levels at ≥4.79 predicted colon cancer recurrence independent of TNM stage IV disease. Larger prospective studies comparing the current assay with standardized methodology are warranted.