Expression of NDRG2 in Human Colorectal Cancer and its Association with Prognosis

Objective: As a member of the N-myc downregulated gene family, N-Myc downstream-regulated gene 2 (NDRG2) contributes to tumorigenesis of various types of cancer. The expression status of NDRG2 in colorectal cancer (CRC) and its prognostic value remain to be elucidated. The goal of this study was to determine the expression pattern of NDRG2 in human CRC and its association of NDRG2 expression with prognosis. Methods: Immunohistochemistry was used to determine the level of NDRG2 expressions in 316 CRC tissues. The medical records of consecutive CRC patients undergoing primary tumor resection from September 2000 to February 2015 were retrospectively selected. Then, we compared to specific clinicopathological features in patients with different level of NDRG2 expressions. The correlation of NDRG2 expression with 3-year survival rate was assessed by Kaplan-Meier method and Cox regression modeling. Results: NDRG2 was expressed in 94.6% (299/316) of CRC tissues. The median IHC score of NDRG2 expression was significantly lower in tumor tissues compared with that of tumor-adjacent normal tissues [4.50(range 0.00-12.00) vs. 10.00 (range 0.00-12.00), P < 0.001].Survival analysis indicated that patients with low NDRG2 expression had poorer 3-year OS than those with high NDRG2 expression (59.9% vs. 76.6%, P = 0.017). Low NDRG2 expression also presented a significantly poorer 3-year OS rate in patient with stage IV disease (29.4% vs. 56.5%, P = 0.002), liver metastasis(32.2% vs. 54.7%, P = 0.005) and those receiving liver resection(56.5% vs. 71.9% , P = 0.012). Multivariate analysis indicated that high NDRG2 expression was independently associated with poor OS (hazard ratio [HR]: 1.499; 95% confidence interval [CI]: 1.037-2.165; P = 0.031). Conclusions: Low expression of NDRG2 was associated with unfavorable prognosis in CRC patients with primary tumor resection. Detection of NDRG2 expression might be useful for providing valuable information of individualized therapy for CRC patients.