食管癌骨桥蛋白表达与肿瘤乏氧微环境相关性的基础与临床研究

发布时间：2018-01-05 04:04

本文关键词：食管癌骨桥蛋白表达与肿瘤乏氧微环境相关性的基础与临床研究　出处：《济南大学》2015年硕士论文　论文类型：学位论文

【摘要】：背景近年来大量研究表明骨桥蛋白(Osteopontin,OPN)在多种恶性肿瘤组织中的表达增高,其过度表达已被证实参与肿瘤的发生和转移,可作为监测患者肿瘤复发,判断患者预后的重要指标。但其与肿瘤乏氧微环境的相关性尚无报道。目的本研究通过建立食管癌裸鼠移植瘤模型,确定组织OPN表达与肿瘤乏氧状态的相关性,通过分析人食管癌原发灶手术标本,明确人组织中OPN的表达水平与肿瘤乏氧状态的相关性,通过食管癌裸鼠移植瘤模型放疗联合乏氧增敏剂(甘氨双唑钠),分析血清OPN浓度与乏氧增敏疗效的相关性。Ps方法第一部分:临床研究:收集我院68例食管癌手术患者术后标本,免疫组化检测标本肿瘤OPN及HIF-1α,分析OPN与HIF-1α表达之间的相关性。第二部分:动物实验:建立食管癌裸鼠移植瘤模型,待肿瘤直径约1cm左右时处死裸鼠。取移植瘤标本,石蜡切片,免疫组化检测组织中OPN与HIF-1α的表达情况。第三部分:乏氧增效研究:建立食管癌裸鼠移植瘤模型,治疗前取荷瘤鼠眼裂血,检测血清中OPN浓度,并将荷瘤鼠分为5组:无治疗组、单纯照射组(5Gy X 6次)、甘氨双唑钠(尾静脉注射高、中、低剂量CMNa)+照射组(5Gy X 6次),监测移植瘤生长情况,绘制肿瘤体积曲线,分析血清中OPN浓度与肿瘤生长关系。结果经Spearman相关分析显示:68例人食管癌患者原发灶中OPN表达与HIF-1α表达有明显相关性(p0.001,r=0.43)。裸鼠移植瘤中OPN与HIF-1α表达具有相关性。裸鼠血清中OPN水平能够预测乏氧增敏疗效。Pfr结论结果表明人与裸鼠移植瘤模型中骨桥蛋白与HIF-1α的相关性,分析显示骨桥蛋白高表达与HIF-1有明显相关(p0.05),对于放疗患者,OPN还可以预测乏氧增敏的疗效。本课题明确了食管癌OPN表达与肿瘤乏氧微环境的相关性,确定OPN表达预测食管癌放疗乏氧增敏的准确性,为患者评价预后及预测疗效提供了参考依据。
[Abstract]:Background in recent years, a large number of studies have shown that osteopontin Osteopontinopontin (OPN) in a variety of malignant tumor tissue expression increased, its overexpression has been proved to be involved in the occurrence and metastasis of tumors. It can be used as an important index for monitoring tumor recurrence and judging the prognosis of patients. However, the correlation between tumor hypoxia microenvironment and tumor recurrence has not been reported. Objective to establish the transplanted tumor model of esophageal carcinoma in nude mice. To determine the correlation between the expression of OPN and the hypoxic state of the tumor, and to determine the correlation between the expression of OPN and the hypoxic state of the tumor by analyzing the surgical specimens of the primary tumor of human esophageal carcinoma. The transplanted tumor model of esophageal carcinoma in nude mice was treated by radiotherapy combined with hypoxia sensitizer (glycosaprazole sodium). Analysis of correlation between serum OPN concentration and anoxic sensitizing effect. Methods part 1: clinical study: 68 postoperative specimens of esophageal cancer patients in our hospital were collected. Immunohistochemistry was used to detect OPN and HIF-1 伪, and to analyze the correlation between OPN and HIF-1 伪 expression. The second part: animal experiment: to establish transplanted tumor model of esophageal carcinoma in nude mice. The nude mice were killed when the tumor diameter was about 1 cm. The transplanted tumor specimens were taken and paraffin sections were taken. Immunohistochemistry was used to detect the expression of OPN and HIF-1 伪 in tissues. Part three: hypoxia synergistic study: establish transplanted tumor model of esophageal carcinoma in nude mice, and take blood from eye fissure of tumor-bearing mice before treatment. The concentration of OPN in serum was measured, and the tumor-bearing mice were divided into 5 groups: no treatment group, simple irradiation group (5 Gy X 6 times), glycine diazole sodium (caudal vein injection high, medium). The growth of transplanted tumor was monitored and the tumor volume curve was drawn in the low dose CMNa irradiation group (5 Gy X 6 times). Results Spearman correlation analysis showed that OPN expression was significantly correlated with HIF-1 伪 expression in 68 patients with esophageal cancer (P < 0.05). P0.001. Ru 0.43). The expression of OPN and HIF-1 伪 in xenografts of nude mice was correlated. The level of OPN in serum of nude mice could predict the effect of hypoxia sensitization. Correlation of HIF-1 伪. The analysis showed that the high expression of osteopontin was significantly correlated with HIF-1 in patients with radiotherapy. OPN can also predict the efficacy of hypoxia sensitization. This study identified the correlation between OPN expression and tumor hypoxia microenvironment in esophageal cancer, and confirmed the accuracy of OPN expression in predicting hypoxia sensitization in esophageal cancer radiotherapy. It provides a reference for patients to evaluate prognosis and predict curative effect.
【学位授予单位】：济南大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R735.1

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