缺氧诱导因子及相关蛋白在鼻咽纤维血管瘤中的表达及与临床预后的相关性研究

发布时间：2018-03-29 11:48

  本文选题：鼻咽纤维血管瘤　切入点：组织芯片　出处：《复旦大学》2014年博士论文

【摘要】：[目的]运用组织芯片技术对JNA中HIF-1α、VEGF、CREG、OPN、c-Src、 STAT3与p-STAT3的表达水平进行检测,联系患者的临床资料,寻找可靠的判断预后的指标。[方法]通过免疫组化染色方法,检测HIF-1α、VEGF、CREG、OPN、c-Src、 STAT3与p-STAT3在70例患者肿瘤样本中的表达水平。镜下估算每个组织阵列点中染色细胞数量占所有细胞数量的百分比,将其按0-25%,26-75%,76-100%划分为1、2、3级；由于每个患者在组织芯片中对应两个连续的组织阵列点,因此将每两个阵列点的表达水平取平均值,所有患者的分级最终分为1、1.5、2、2.5、3共5个分级；先估计所有细胞的表达水平,再分别估计内皮细胞、间质细胞的表达水平。统计分析患者临床资料,包括年龄、术中出血量、肿瘤分期、术后复发时间,及血管密度,与各分子表达水平分级之间的相关性。[结果]STAT3、p-STAT3在所有样本及对照组中均无阳性表达；HIF-1α、VEGF、 c-Src、 OPN与CREG在内皮细胞、间质细胞中均表达阳性,且各个蛋白表达水平互相相关；此外,内皮细胞中该五种蛋白的表达水平与微血管密度相关。分子表达水平与临床数据之间的相关性分析发现：1、年龄较小的患者(≤17岁)HIF-1α、 VEGF、CREG、c-Src表达水平较高；2、Radkowski分期及术中出血量未表现出与HIF-1α、VEGF、c-Src、OPN及CREG表达水平之间的联系。3、复发患者肿瘤内皮细胞中高表达HIF-1α(p值：0.010.05)；内皮细胞HIF-1α高表达组的无瘤生存时间较低水平表达组明显缩短(低水平表达组均值：107.038个月；高水平表达组均值：66.448个月；p值：0.0060.05)。最后,经过ROC曲线检验,内皮细胞HIF-1a表达水平作为判断复发的指标,效能较好(曲线下面积为0.697,p值为0.015)[结论]STAT3、p-STAT3并不参与JNA发生发展的调控；HIF-1α、VEGF、 CREG、OPN与c-Src可能通过协同作用,促进肿瘤的生长及血管形成；这些蛋白在内皮细胞中的表达水平与血管密度高度相关,提示JNA内皮细胞倾向于通过自分泌作用促进血管形成；HIF-1α VEGF、CREG、c-Src与年龄分组相关,这与JNA越年轻的患者预后往往越差的现象一致；JNA内皮细胞HIF-1α表达水平或可作为判断患者术后复发的有效指标。
[Abstract]:[objective] to detect the expression levels of HIF-1 伪 -VEGFU, STAT3 and p-STAT3 in JNA by tissue chip technique, and to find a reliable prognostic index by means of immunohistochemical staining, according to the clinical data of the patients. The expression levels of HIF-1 伪 -VEGFU, STAT3 and p-STAT3 were detected in 70 tumor samples. The percentage of stained cells in each tissue array was estimated under microscope, and the cells were divided into 2 groups according to 0-2526 ~ 7575 ~ 76-100%. Because each patient corresponds to two consecutive tissue array points in the tissue microarray, the average expression level of each two array points is taken as the average, and all patients' grades are finally divided into 5 grades: 1 / 1. 5 / 2 / 2 / 2 / 5 / 3; first, estimate the expression level of all cells. The expression levels of endothelial cells and interstitial cells were estimated respectively. The clinical data including age, intraoperative bleeding volume, tumor stage, postoperative recurrence time, and vascular density were statistically analyzed. [results] there was no positive expression of STAT3 p-STAT3 in all samples and controls. HIF-1 伪 -VEGF, c-Src, OPN and CREG were positive in endothelial cells and interstitial cells, and the expression levels of each protein were related to each other. The expression level of these five proteins was correlated with microvessel density in endothelial cells. The correlation between the molecular expression level and clinical data was analyzed. The results showed that the expression level of the five proteins was higher in the younger patients (鈮，

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