Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Cancer Lett. 2011 Nov 1;310(1):35-45. doi: 10.1016/j.canlet.2011.06.001. Epub 2011 Jun 24.
N-myc downstream-regulated gene 1 (NDRG1) has been reported to be a multifunctional protein associated with carcinogenesis, however, the cellular function of NDRG1 remains elusive in human cancers. Here, our proteomics profile analysis of HCC tissues with different metastatic capabilities revealed that NDRG1 was correlated with metastasis and recurrence in HCC patients after liver transplantation (LT). Immunohistochemical staining of 143 HCC patients after LT showed that NDRG1-positive expression had poor prognosis, either for shorter disease-free survival or overall survival (P < 0.001), compared with NDRG1-negative expression. Multivariate analysis confirmed NDRG1 as an independent prognostic value (P < 0.001). In addition, in vitro experiments HCC cells with small interfering RNA against NDRG1 significantly suppressed its proliferation, colony formation, invasion and migration ability. Microarray analysis revealed that NDRG1 modulated the expression of genes associated with transmembrane transporter activity, chemoattractant activity, immune response, cell adhesion and cell proliferation process. Taken together, these results suggested that NDRG1 was an important molecule in controlling HCC metastasis and thus suggested as a novel biomarker for predicting HCC recurrence after LT.
N- MYC 下游调节基因 1（NDRG1）已被报道为一种与致癌作用相关的多功能蛋白，然而，其在人类癌症中的细胞功能仍不清楚。在这里，我们对具有不同转移能力的 HCC 组织的蛋白质组学分析显示，NDRG1 与 HCC 患者肝移植（LT）后的转移和复发相关。对 143 例 LT 后 HCC 患者的免疫组织化学染色显示，与 NDRG1 阴性表达相比，NDRG1 阳性表达的患者无病生存率或总生存率较差（P <0.001）。多变量分析证实 NDRG1 是独立的预后指标（P <0.001）。此外，在体外实验中，针对 NDRG1 的小干扰 RNA 的 HCC 细胞显著抑制其增殖、集落形成、侵袭和迁移能力。微阵列分析显示，NDRG1 调节与跨膜转运体活性、趋化活性、免疫反应、细胞黏附和细胞增殖过程相关的基因的表达。综上所述，这些结果表明 NDRG1 是控制 HCC 转移的重要分子，因此可以作为预测 LT 后 HCC 复发的新型生物标志物。
