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食管胃结合部癌组织KIF2A和MT1-MMP表达相关性与临床意义

发布时间:2018-12-31 19:21
【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,P0.01。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,P0.01。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P0.05。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,P0.05。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,P0.05。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,P0.01。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。
[Abstract]:Objective to investigate the role of kinesinsuperfamily proteins,KIF2A and MMP 1 (membrane type 1-matrix metalloproteinase,MT1-MMP in the development of various tumors. However, the expression of KIF2A and MT1-MMP in esophageal and gastric junction carcinoma (adenocarcinoma of esophagastric junction,AEG) was less studied. This study will investigate the clinical significance of the expression of KIF2A and MT1-MMP in AEG and their correlation. Methods the paraffin tissues of 172 patients with AEG were collected from Thoracic surgery Department affiliated Cancer Hospital of Xinjiang Medical University. The expression of KIF2A and MT1-MMP mRNA were detected by RT-PCR method in 42 fresh AEG tissues and 20 paracancerous tissues. The expression of KIF2A and MT1-MMP in paraffin wax was detected by immunohistochemical method. To analyze the correlation between the expression of KIF2A and MT1-MMP and the clinicopathological features, the influence on the prognosis of AEG patients and the correlation between them. Results the expression of KIF2A and MT1-MMP mRNA in AEG was significantly up-regulated, especially in AEG patients with lymph node metastasis, and the difference was statistically significant compared with that in paracancerous tissues (P0.01). The positive expression rates of KIF2A and MT1-MMP protein were 68.6% and 63.9% in 172 cases of AEG, respectively, which were significantly higher than those in adjacent tissues. The expression levels of P0.01.KIF2A and MT1-MMP protein were significantly higher than those of TNM stage of AEG. Lymph node metastasis, degree of differentiation, depth of invasion and distant metastasis were significantly lower in patients with positive expression of P0.05.KIF2A and MT1-MMP than in patients with negative lymph node metastasis, and there was significant difference between 3-year and 5-year survival rates. Multivariate analysis of P0.05.Cox regression model showed that TNM stage, lymph node metastasis, depth of invasion, KIF2A and MT1-MMP expression were independent risk factors for the overall survival rate of AEG patients, P0.05.KIF2A positive AEG patients. The positive rate of MT1-MMP was also significantly increased, 92 (77.97%) of the 118 AEG patients with KIF2A positive were MT1-MMP positive, and there was a significant positive correlation between the quantitative level of mRNA and the quantitative level of mRNA (r = 0.562, P 0.01). Conclusion the co-expression of KIF2A and MT1-MMP is closely related to the occurrence and development of AEG, which may be an independent risk factor for the prognosis of AEG and a target for gene therapy.
【作者单位】: 新疆医科大学附属肿瘤医院胸外科;新疆医科大学基础医学院药理学教研室;
【基金】:国家自然科学基金(81360491) 新疆自治区自然科学基金(2016D01C369)
【分类号】:R735


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