Department of Respiratory Medicine, First Affiliated Hospital of Zhengzhou University, No. 1. Jianshe East Road, Zhongyuan District, Zhengzhou, 450052, Henan, People's Republic of China.
Med Oncol. 2012 Dec;29(4):2654-60. doi: 10.1007/s12032-012-0213-0. Epub 2012 Mar 24.
Neural precursor cell expressed, developmentally downregulated 9 (NEDD9) acts as a scaffold protein and belongs to a family of CAS (Crk-associated substrate) that regulates protein complexes controlling invasion and differentiation. Preclinical research for this gene was predominantly reported in melanomas, glioblastoma, and lymphoma. So we investigated the expression and significance of NEDD9 mRNA and protein in lung tissues. Specifically, we immunohistochemically compared NEDD9 expression and localization in 24 formalin-fixed and paraffin-embedded lung adenocarcinoma tissues with that of surrounding nonneoplastic tissue and five microscopically normal lungs. NEDD9 mRNA levels were quantitatively analyzed by fluorescent quantitative reverse transcription-polymerase chain reaction (FQ-PCR) in frozen tissue specimens of all tumors and 24 matched nonneoplastic lung parenchymas, and protein expression in 16 homogenates of matched neoplastic/nonneoplastic specimens was evaluated by Western blotting. The three techniques showed that NEDD9 is weakly expressed in nonneoplastic lung parenchyma and upregulated in lung adenocarcinoma. Moreover, FQ-PCR indicated a statistically significant correlation between NEDD9 upregulation and higher disease stages (I+II versus III+IV, p=0.001; high and middle versus low differentiation, p<0.001). Our results provide evidence that NEDD9 is upregulated in lung adenocarcinoma, and overexpression of NEDD9 protein has been strongly correlated with staging and differentiation grade and tumor size in lung adenocarcinoma, which demonstrated a poor prognosis.
神经前体细胞表达,发育下调 9(NEDD9)作为支架蛋白,属于 CAS(Crk 相关底物)家族,调节控制侵袭和分化的蛋白质复合物。该基因的临床前研究主要在黑色素瘤、神经胶质瘤和淋巴瘤中报道。因此,我们研究了 NEDD9mRNA 和蛋白在肺组织中的表达和意义。具体来说,我们通过免疫组织化学比较了 24 例福尔马林固定和石蜡包埋的肺腺癌组织中 NEDD9 的表达和定位,与周围非肿瘤组织和 5 例显微镜下正常肺组织进行了比较。通过荧光定量逆转录聚合酶链反应(FQ-PCR)对所有肿瘤和 24 例匹配的非肿瘤性肺实质的冷冻组织标本进行了 NEDD9mRNA 水平的定量分析,并通过 Western blotting 评估了 16 例匹配的肿瘤/非肿瘤标本的蛋白质表达。这三种技术均表明,NEDD9 在非肿瘤性肺实质中表达较弱,在肺腺癌中上调。此外,FQ-PCR 表明 NEDD9 的上调与较高的疾病分期(I+II 期与 III+IV 期,p=0.001;高和中分化与低分化,p<0.001)之间存在统计学显著相关性。我们的研究结果表明,NEDD9 在肺腺癌中上调,并且 NEDD9 蛋白的过表达与肺腺癌的分期和分化程度以及肿瘤大小密切相关,表明预后不良。