【摘要】：目的驅(qū)動蛋白超家族2A(kinesinsuperfamily proteins,KIF2A)和膜型基質(zhì)金屬蛋白酶1(membrane type 1-matrix metalloproteinase,MT1-MMP)在多種腫瘤的發(fā)生、發(fā)展中具有一定的關(guān)聯(lián)作用。但對于食管胃結(jié)合部癌(adenocarcinoma of esophagastric junction,AEG)中KIF2A和MT1-MMP表達(dá)的研究較少。本研究將探討KIF2A和MT1-MMP在AEG中表達(dá)的臨床意義及其兩者的相關(guān)性。方法收集新疆醫(yī)科大學(xué)附屬腫瘤醫(yī)院胸外科收治的172例AEG患者的腫瘤組織和對應(yīng)的癌旁組織石蠟標(biāo)本,同時收集其中新鮮的AEG組織標(biāo)本42例和癌旁組織20例。RT-PCR法檢測新鮮組織中KIF2A和MT1-MMP mRNA表達(dá)。免疫組化法檢測石蠟標(biāo)本中KIF2A和MT1-MMP蛋白表達(dá)。分析KIF2A和MT1-MMP表達(dá)水平與臨床病理特征的相關(guān)性,及其對AEG患者預(yù)后的影響和兩者之間的相關(guān)性。結(jié)果 AEG組織中的KIF2A和MT1-MMP mRNA表達(dá)水平均顯著上調(diào),其中發(fā)生淋巴結(jié)轉(zhuǎn)移的AEG患者中兩者上調(diào)的程度更強(qiáng),與癌旁組織相比,差異有統(tǒng)計學(xué)意義,P0.01。在172例AEG腫瘤組織中,KIF2A和MT1-MMP蛋白陽性表達(dá)率分別為68.6%和63.9%,均顯著高于癌旁組織,差異有統(tǒng)計學(xué)意義,P0.01。KIF2A和MT1-MMP蛋白的表達(dá)水平與AEG的TNM分期、淋巴結(jié)轉(zhuǎn)移、分化程度、浸潤深度和遠(yuǎn)處轉(zhuǎn)移有關(guān),均P0.05。KIF2A和MT1-MMP陽性表達(dá)患者的生存率明顯低于陰性患者,其中3年與5年生存率之間差異有統(tǒng)計學(xué)意義,P0.05。Cox回歸模型多因素分析表明,TNM分期、淋巴結(jié)轉(zhuǎn)移、浸潤深度、KIF2A和MT1-MMP表達(dá)水平是影響AEG患者術(shù)后總生存率的獨(dú)立危險因素,P0.05。KIF2A陽性的AEG患者中,MT1-MMP的陽性率也明顯增加,KIF2A陽性的118例AEG患者中有92例(77.97%)MT1-MMP呈陽性,兩者之間mRNA定量水平之間也呈現(xiàn)出明顯的正相關(guān)性,r=0.562,P0.01。結(jié)論KIF2A和MT1-MMP的協(xié)同高表達(dá)與AEG的發(fā)生、發(fā)展密切相關(guān),其可能成為AEG預(yù)后的獨(dú)立危險因素和基因治療的靶標(biāo)。
[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.
【作者單位】： 新疆醫(yī)科大學(xué)附屬腫瘤醫(yī)院胸外科;新疆醫(yī)科大學(xué)基礎(chǔ)醫(yī)學(xué)院藥理學(xué)教研室;
【基金】：國家自然科學(xué)基金(81360491) 新疆自治區(qū)自然科學(xué)基金(2016D01C369)
【分類號】：R735
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本文編號：2397010