食管胃结合部癌组织KIF2A和MT1-MMP表达相关性与临床意义  

Clinical significance and correlation of KIF2A and MT1-MMP expression in adenocarcinoma of esophagastric junction

作　　者：罗洞波[1] 高云飞[1] 吕红博[1] 初建虎[1] 孙晓宏[1] 程路峰[2] L UO Dong-bo GAO Yun-fei LU Hong-bo CHU Jian-hul SUN Xiao-hong CHENG Lu-feng(Department of Thoracic Surgery ,Affiliated Tumor Hospital of Xinjiang Medical University, Urumqi 830011,P. R. China Department of Pharmacology, School of Preclinical Medicine of Xinjiang Medical University, Urumqi 830011,P. R. China)

机构地区：[1]新疆医科大学附属肿瘤医院胸外科,新疆乌鲁木齐830011 [2]新疆医科大学基础医学院药理学教研室,新疆乌鲁木齐830011

出　　处：《中华肿瘤防治杂志》2017年第13期894-900,共7页Chinese Journal of Cancer Prevention and Treatment

基　　金：国家自然科学基金(81360491);新疆自治区自然科学基金(2016D01C369)

摘　　要：目的驱动蛋白超家族2A(kinesinsuperfamily proteins,KIF2A)和膜型基质金属蛋白酶1(membrane type 1-matrix metalloproteinase,MT1-MMP)在多种肿瘤的发生、发展中具有一定的关联作用。但对于食管胃结合部癌(adenocarcinoma of esophagastric junction,AEG)中KIF2A和MT1-MMP表达的研究较少。本研究将探讨KIF2A和MT1-MMP在AEG中表达的临床意义及其两者的相关性。方法收集新疆医科大学附属肿瘤医院胸外科收治的172例AEG患者的肿瘤组织和对应的癌旁组织石蜡标本,同时收集其中新鲜的AEG组织标本42例和癌旁组织20例。RT-PCR法检测新鲜组织中KIF2A和MT1-MMP mRNA表达。免疫组化法检测石蜡标本中KIF2A和MT1-MMP蛋白表达。分析KIF2A和MT1-MMP表达水平与临床病理特征的相关性,及其对AEG患者预后的影响和两者之间的相关性。结果 AEG组织中的KIF2A和MT1-MMP mRNA表达水平均显著上调,其中发生淋巴结转移的AEG患者中两者上调的程度更强,与癌旁组织相比,差异有统计学意义,P<0.01。在172例AEG肿瘤组织中,KIF2A和MT1-MMP蛋白阳性表达率分别为68.6%和63.9%,均显著高于癌旁组织,差异有统计学意义,P<0.01。KIF2A和MT1-MMP蛋白的表达水平与AEG的TNM分期、淋巴结转移、分化程度、浸润深度和远处转移有关,均P<0.05。KIF2A和MT1-MMP阳性表达患者的生存率明显低于阴性患者,其中3年与5年生存率之间差异有统计学意义,P<0.05。Cox回归模型多因素分析表明,TNM分期、淋巴结转移、浸润深度、KIF2A和MT1-MMP表达水平是影响AEG患者术后总生存率的独立危险因素,P<0.05。KIF2A阳性的AEG患者中,MT1-MMP的阳性率也明显增加,KIF2A阳性的118例AEG患者中有92例(77.97%)MT1-MMP呈阳性,两者之间mRNA定量水平之间也呈现出明显的正相关性,r=0.562,P<0.01。结论KIF2A和MT1-MMP的协同高表达与AEG的发生、发展密切相关,其可能成为AEG预后的独立危险因素和基因治疗的靶标。OBJECTIVE The kinetin superfamily 2A （KIF2A） and membrane type 1-matrix metalloproteinase （MT1-MMP） have a certain correlation in the development and progression of various tumors. However, there is littleresearch on the expression of KIF2A and MT1-MMP in adenocarcinoma of esophagastric junction （AEG）. This study will investigate the clinical significance and interrelation of KIF2A and MT1-MMP expression in AEG. METHODS The par- affin-embedded specimens of tumor tissues and adjacent tissues of 172 AEG patients were collected from thoracic surgery of our hospital. At the same time,the fresh specimens of 24 AEG tissues and 20 cases of adjacent tissues were also col- lected. RT-PCR was used to detect the expression of KIF2A and MT1-MMP mRNA in fresh tissues. Immunohistochem- istry was used to detect the expression of KIF2A and MT1-MMP protein in paraffin specimens. Moreover, the relation- ship between the expression of KIF2A, MT1-MMP and clinicopathological features was analyzed, and then the prognosis of AEG patients and correlation of KIF2A and MT1-MMP were also analyzed. RESULTS The level of KIF2A and MT1-MMP mRNA was significantly up-regulated in AEG tissues, and there was a significant difference compared with adjacent tissues （P〈0.01）. The positive rates of KIF2A and MT1-MMP were 68.6% and 63.9% in 172 cases AEG pa- tients, respectively,which were significantly higher than those in the adjacent normal tissues （P〈0.01）, and the expres- sion level of KIF2A and MT1-MMP was related to TNM stage,lymph node metastasis,differentiation degree,depth of in- vasion and distant metastasis of AEG （P〈0.05）. The survival rate of patients with high expression of KIF2A and MT1- MMP was significantly lower than that of patients with low expression,and the difference between 3 and 5-year survival rates was statistically significant （P〈0.05）. Cox regression analysis showed that TNM stage,lymph node metastasis, depth of invasion,and expression of KIF2A and MT1-MMP were independent risk factors f

关 键 词：食管胃结合部癌 驱动蛋白超家族2A 膜型基质金属蛋白酶1 病理特征 预后 

分 类 号：R735[医药卫生—肿瘤]