Identification of high-risk stage II colorectal tumors by combined analysis of the NDRG1 gene expression and the depth of tumor invasion.

BACKGROUND

Experiments on cancer cell lines and animal models indicated that alteration in expression of N-myc down-regulated gene 1 (NDRG1) is associated with development of colon cancer. However, few clinical data are available to assess the role of NDRG1 in progression of human colorectal cancer. This study was undertaken to reveal the prognostic and predictive usefulness of NDRG1 expression determination in colorectal cancer.

METHODS

The expression of NDRG1 mRNA was investigated in 108 colorectal cancer tissues by real-time polymerase chain reaction. The level of NDRG1 protein was investigated by immunohistochemistry.

RESULTS

Patients with lowered level of NDRG1 mRNA had a statistically significantly shorter 5-year survival rate compared with patients with unchanged expression of NDRG1 (P = .01). The overall survival time for patients with II tumor, node, metastasis system (TNM) stage disease and tumors displaying reduced expression of NDRG1 was significantly shorter compared with patients with preserved NDRG1 expression (P = .024). Moreover, the survival rate of patients with TNM stage II disease and T4 lesion was significantly lower (P = .0005) for patients with reduced level of NDRG1 expression compared with patients with unchanged NDRG1 expression. The stepwise multivariate regression analysis revealed that advanced TNM stage and lowered NDRG1 expression level were independent unfavorable prognostic factors for patient survival.

CONCLUSIONS

The assessment of NDRG1 expression offers valuable prognostic information for patients with colorectal cancer, especially for those with stage II disease. We propose that NDRG1 expression level could be used to select patients with stage II disease who are at increased risk of unfavorable outcome, and who may benefit from adjuvant therapy.