Chen Wenjing, Peng Jianhong, Ou Qingjian, Wen Yongshan, Jiang Wu, Deng Yuxiang, Zhao Yujie, Wan Desen, Pan Zhizhong, Fang Yujing
Department of Clinical Laboratory, the First Affiliated Hospital, Jinan University, Guangzhou 510630, China.
Department of Colorectal Surgery, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong 510060, P. R. China.
J Cancer. 2019 Jun 9;10(15):3373-3380. doi: 10.7150/jca.31382. eCollection 2019.
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. 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. 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). 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.
作为N - myc下调基因家族的一员，N - Myc下游调控基因2（NDRG2）在多种癌症的肿瘤发生过程中发挥作用。NDRG2在结直肠癌（CRC）中的表达状态及其预后价值仍有待阐明。本研究的目的是确定NDRG2在人类CRC中的表达模式及其与预后的关系。采用免疫组织化学方法检测316例CRC组织中NDRG2的表达水平。回顾性选取2000年9月至2015年2月接受原发性肿瘤切除的连续CRC患者的病历。然后，我们比较了不同NDRG2表达水平患者的特定临床病理特征。采用Kaplan - Meier法和Cox回归模型评估NDRG2表达与3年生存率的相关性。NDRG2在94.6%（299/316）的CRC组织中表达。与肿瘤邻近正常组织相比，肿瘤组织中NDRG2表达的免疫组化中位评分显著降低[4.50（范围0.00 - 12.00）对10.00（范围0.00 - 12.00），P < 0.001]。生存分析表明，NDRG2低表达患者的3年总生存率低于高表达患者（59.9%对76.6%，P = 0.017）。NDRG2低表达在IV期疾病患者（29.4%对56.5%，P = 0.002）、肝转移患者（32.2%对54.7%，P = 0.005）以及接受肝切除的患者（56.5%对71.9%，P = 0.012）中也呈现出显著较差的3年总生存率。多因素分析表明，NDRG2高表达与较差的总生存期独立相关（风险比[HR]：1.499；95%置信区间[CI]：1.037 - 2.165；P = 0.031）。NDRG2低表达与接受原发性肿瘤切除的CRC患者的不良预后相关。检测NDRG2表达可能有助于为CRC患者提供个体化治疗的有价值信息。
