Wang Xinhua, Liu Hongling, Wang Xiaoyu, An Yuzhi
Department of Oncology, The First Affiliated Hospital of Liaoning Medical University, Jinzhou, Liaoning 121000, P.R. China.
Department of Respiratory Internal Medicine, Qingzhou People's Hospital, Qinzhou, Shandong 262500, P.R. China.
Oncol Lett. 2014 Dec;8(6):2417-2422. doi: 10.3892/ol.2014.2526. Epub 2014 Sep 12.
Migration and invasion inhibitor protein (MIIP) was initially identified in a yeast two-hybrid screen. Recently, MIIP has emerged as a key protein in regulating cell migration and invasion. However, the MIIP expression profile in non-small-cell lung cancer (NSCLC) has not been analyzed. In the present study, MIIP mRNA expression levels were evaluated using the SYBR Green quantitative real-time polymerase chain reaction method in 37 NSCLC specimens and matched normal tissue samples. MIIP protein expression in a further 94 NSCLC specimens was examined with immunohistochemistry. Patient survival data were collected retrospectively, and the association between MIIP protein expression and the five-year overall survival rate was evaluated. The results revealed that MIIP mRNA and protein expression were downregulated in cancer tissues, as compared with the matched normal tissues. MIIP expression levels were significantly associated with pathology and tumor stage, with reduced MIIP mRNA expression levels detected in advanced tumor stage samples. Furthermore, patients with MIIP-positive protein expression had an improved prognosis as compared with those patients with MIIP-negative protein expression, with five-year survival rates of 41.7 and 22.4%, respectively (Kaplan-Meier, log-rank, P=0.028). A significant association between MIIP protein expression and improved prognosis was also demonstrated using univariate and multivariate analyses (P=0.033 and P=0.040, respectively). These results suggest that MIIP may have a potential role in the pathogenesis of NSCLC and also confirm that MIIP is a putative tumor-suppressor gene. Therefore, MIIP may be identified as a functional genetic marker of NSCLC development and prognosis, and may be an attractive therapeutic target for the treatment of lung cancer.
迁移和侵袭抑制蛋白（MIIP）最初是在酵母双杂交筛选中被鉴定出来的。最近，MIIP已成为调节细胞迁移和侵袭的关键蛋白。然而，非小细胞肺癌（NSCLC）中MIIP的表达谱尚未得到分析。在本研究中，采用SYBR Green定量实时聚合酶链反应方法评估了37例NSCLC标本及配对正常组织样本中MIIP mRNA的表达水平。另外，用免疫组织化学方法检测了94例NSCLC标本中MIIP蛋白的表达。回顾性收集患者生存数据，并评估MIIP蛋白表达与五年总生存率之间的关联。结果显示，与配对的正常组织相比，癌组织中MIIP mRNA和蛋白表达下调。MIIP表达水平与病理及肿瘤分期显著相关，在晚期肿瘤样本中检测到MIIP mRNA表达水平降低。此外，MIIP蛋白表达阳性的患者与MIIP蛋白表达阴性的患者相比，预后有所改善，五年生存率分别为41.7%和22.4%（Kaplan-Meier法，对数秩检验，P=0.028）。单因素和多因素分析也显示MIIP蛋白表达与预后改善之间存在显著关联（分别为P=0.033和P=0.040）。这些结果表明，MIIP可能在NSCLC的发病机制中具有潜在作用，也证实MIIP是一种假定的肿瘤抑制基因。因此，MIIP可能被确定为NSCLC发生发展和预后的功能性遗传标志物，并且可能是肺癌治疗中一个有吸引力的治疗靶点。
