State Key Laboratory of Cancer Biology, Department of Gastrointestinal Surgery, Xijing Hospital, The Fourth Military Medical University, Xi'an, China.
Cancer Sci. 2010 May;101(5):1292-9. doi: 10.1111/j.1349-7006.2010.01529.x. Epub 2010 Feb 11.
N-Myc downstream-regulated gene 2 (NDRG2), a new member of the N-Myc downstream-regulated gene family, has been found to be a differentially expressed gene involved in a variety of cancers. The present study aimed to investigate the expression of NDRG2 in esophageal squamous cell carcinoma (ESCC). Immunohistochemistry was performed in 154 samples from patients with ESCC to detect the expression level of NDRG2 and C-MYC. Results indicated that the expression level of NDRG2 in the cancer samples was significantly lower than that in normal tissues; the trend of C-MYC was the reverse. The Wilcoxon-Mann-Whitney test showed significant difference in the expression of NDRG2 in patients with different T stage, TNM stage, and differentiation degree of cancers (P = 0.036, 0.031, 0.001, respectively). Patients in stages I and II were followed up for 5 consecutive years and Kaplan-Meier survival analysis demonstrated that the survival time of ESCC patients with high expression of NDRG2 was longer than those with low expression during the 5-year follow-up period (P = 0.0018). Cox regression analysis indicated that low expression of NDRG2, cancer stage of pT1, and distant organ metastasis (pM1) were the independent poor prognostic factors of ESCC (P = 0.004, 0.019, 0.0013, respectively). Furthermore, up-regulation of NDRG2 was introduced to ESCC cell lines (EC9706 and EC109) by plasmid transfection. In vivo and in vitro studies indicated that overexpression of NDRG2 markedly reduced proliferation and promoted the apoptosis of EC9706 and EC109 cells. In summary, our results demonstrated that NDRG2 played an important role in the proliferation of ESCC cells and the expression of NDRG2 in ESCC was closely related with the prognosis.
N- MYC 下游调节基因 2（NDRG2）是 N-MYC 下游调节基因家族的新成员，已被发现是一种参与多种癌症的差异表达基因。本研究旨在探讨 NDRG2 在食管鳞状细胞癌（ESCC）中的表达。对 154 例 ESCC 患者的样本进行免疫组织化学检测，以检测 NDRG2 和 C-MYC 的表达水平。结果表明，癌症样本中 NDRG2 的表达水平明显低于正常组织；C-MYC 的趋势相反。Wilcoxon-Mann-Whitney 检验显示，不同 T 分期、TNM 分期和癌症分化程度患者的 NDRG2 表达差异有统计学意义（P=0.036，0.031，0.001）。I 期和 II 期患者连续随访 5 年，Kaplan-Meier 生存分析显示，NDRG2 高表达的 ESCC 患者的生存时间长于 5 年随访期间低表达的患者（P=0.0018）。Cox 回归分析表明，NDRG2 低表达、pT1 期癌症和远处器官转移（pM1）是 ESCC 的独立不良预后因素（P=0.004，0.019，0.0013）。此外，通过质粒转染将 NDRG2 上调至 ESCC 细胞系（EC9706 和 EC109）。体内和体外研究表明，NDRG2 的过表达显著降低了 EC9706 和 EC109 细胞的增殖，并促进了其凋亡。综上所述，我们的研究结果表明，NDRG2 在 ESCC 细胞的增殖中发挥重要作用，NDRG2 在 ESCC 中的表达与预后密切相关。
