Lu Peng, Wang Zhi-Peng, Dang Zheng, Zheng Zhi-Gang, Li Xiao, Zhou Liang, Ding Rui, Yue Shu-Qiang, Dou Ke-Feng
Department of Hepatobiliary and Pancreaticosplenic Surgery, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shanxi, P.R. China.
Department of Pharmacology, School of Pharmacy, The Fourth Military Medical University, Xi'an, Shanxi, P.R. China.
Oncol Rep. 2015 May;33(5):2375-83. doi: 10.3892/or.2015.3863. Epub 2015 Mar 18.
Neural precursor cell expressed, developmentally downregulated 9 (NEDD9) plays an integral role in natural and pathological cell biology. Overexpression of NEDD9 protein has been correlated with poor prognosis in various types of cancer. However, few available data address the precise function of the NEDD9 gene in hepatocellular carcinoma (HCC). In the present study, we investigated NEDD9 expression in 40 primary human HCC tissues compared with matched adjacent non-tumor hepatic tissues using RT-qPCR and western blot analysis. Immunohistochemistry was performed to analyze the correlations between NEDD9 expression and clinicopathological factors. Statistical analyses were applied to derive prognostic values of NEDD9 in HCC. The results showed that the NEDD9 mRNA and protein expression levels in HCC tissues were significantly higher than those in matched adjacent non-tumor hepatic tissues. High NEDD9 expression was correlated with larger tumor size, advanced tumor grade, metastasis, intrahepatic venous invasion and high UICC TNM stages in HCC patients. Patients with high NEDD9 expression levels exhibited poorer recurrence-free and overall survival than those with a low NEDD9 expression. Additionally, NEDD9 expression status was an independent prognostic factor for survival. This correlation remained significant in patients with early-stage HCC or with normal serum AFP levels. The results of this study suggest that NEDD9 may be a valuable prognostic biomarker for HCC, including early-stage and AFP-normal patients.
神经前体细胞表达、发育下调基因9（NEDD9）在正常和病理细胞生物学中发挥着不可或缺的作用。NEDD9蛋白的过表达与多种癌症的不良预后相关。然而，关于NEDD9基因在肝细胞癌（HCC）中的确切功能，现有数据较少。在本研究中，我们采用逆转录定量聚合酶链反应（RT-qPCR）和蛋白质免疫印迹分析，比较了40例原发性人类HCC组织及其配对的癌旁非肿瘤肝组织中NEDD9的表达情况。通过免疫组织化学分析NEDD9表达与临床病理因素之间的相关性。应用统计学分析得出NEDD9在HCC中的预后价值。结果显示，HCC组织中NEDD9的mRNA和蛋白表达水平显著高于其配对的癌旁非肿瘤肝组织。HCC患者中，NEDD9高表达与肿瘤体积较大、肿瘤分级较高、转移、肝内静脉侵犯以及国际抗癌联盟（UICC）TNM分期较高相关。NEDD9表达水平高的患者与NEDD9低表达患者相比，无复发生存率和总生存率更低。此外，NEDD9表达状态是生存的独立预后因素。这种相关性在早期HCC患者或血清甲胎蛋白（AFP）水平正常的患者中仍然显著。本研究结果表明，NEDD9可能是HCC的一个有价值的预后生物标志物，包括早期和AFP正常的患者。
