發(fā)布時間：2018-03-29 11:48

  本文選題：鼻咽纖維血管瘤　切入點：組織芯片　出處：《復(fù)旦大學(xué)》2014年博士論文

【摘要】：[目的]運用組織芯片技術(shù)對JNA中HIF-1α、VEGF、CREG、OPN、c-Src、 STAT3與p-STAT3的表達(dá)水平進(jìn)行檢測,聯(lián)系患者的臨床資料,尋找可靠的判斷預(yù)后的指標(biāo)。[方法]通過免疫組化染色方法,檢測HIF-1α、VEGF、CREG、OPN、c-Src、 STAT3與p-STAT3在70例患者腫瘤樣本中的表達(dá)水平。鏡下估算每個組織陣列點中染色細(xì)胞數(shù)量占所有細(xì)胞數(shù)量的百分比,將其按0-25%,26-75%,76-100%劃分為1、2、3級；由于每個患者在組織芯片中對應(yīng)兩個連續(xù)的組織陣列點,因此將每兩個陣列點的表達(dá)水平取平均值,所有患者的分級最終分為1、1.5、2、2.5、3共5個分級；先估計所有細(xì)胞的表達(dá)水平,再分別估計內(nèi)皮細(xì)胞、間質(zhì)細(xì)胞的表達(dá)水平。統(tǒng)計分析患者臨床資料,包括年齡、術(shù)中出血量、腫瘤分期、術(shù)后復(fù)發(fā)時間,及血管密度,與各分子表達(dá)水平分級之間的相關(guān)性。[結(jié)果]STAT3、p-STAT3在所有樣本及對照組中均無陽性表達(dá)；HIF-1α、VEGF、 c-Src、 OPN與CREG在內(nèi)皮細(xì)胞、間質(zhì)細(xì)胞中均表達(dá)陽性,且各個蛋白表達(dá)水平互相相關(guān)；此外,內(nèi)皮細(xì)胞中該五種蛋白的表達(dá)水平與微血管密度相關(guān)。分子表達(dá)水平與臨床數(shù)據(jù)之間的相關(guān)性分析發(fā)現(xiàn)：1、年齡較小的患者(≤17歲)HIF-1α、 VEGF、CREG、c-Src表達(dá)水平較高；2、Radkowski分期及術(shù)中出血量未表現(xiàn)出與HIF-1α、VEGF、c-Src、OPN及CREG表達(dá)水平之間的聯(lián)系。3、復(fù)發(fā)患者腫瘤內(nèi)皮細(xì)胞中高表達(dá)HIF-1α(p值：0.010.05)；內(nèi)皮細(xì)胞HIF-1α高表達(dá)組的無瘤生存時間較低水平表達(dá)組明顯縮短(低水平表達(dá)組均值：107.038個月；高水平表達(dá)組均值：66.448個月；p值：0.0060.05)。最后,經(jīng)過ROC曲線檢驗,內(nèi)皮細(xì)胞HIF-1a表達(dá)水平作為判斷復(fù)發(fā)的指標(biāo),效能較好(曲線下面積為0.697,p值為0.015)[結(jié)論]STAT3、p-STAT3并不參與JNA發(fā)生發(fā)展的調(diào)控；HIF-1α、VEGF、 CREG、OPN與c-Src可能通過協(xié)同作用,促進(jìn)腫瘤的生長及血管形成；這些蛋白在內(nèi)皮細(xì)胞中的表達(dá)水平與血管密度高度相關(guān),提示JNA內(nèi)皮細(xì)胞傾向于通過自分泌作用促進(jìn)血管形成；HIF-1α VEGF、CREG、c-Src與年齡分組相關(guān),這與JNA越年輕的患者預(yù)后往往越差的現(xiàn)象一致；JNA內(nèi)皮細(xì)胞HIF-1α表達(dá)水平或可作為判斷患者術(shù)后復(fù)發(fā)的有效指標(biāo)。
[Abstract]:[objective] to detect the expression levels of HIF-1 偽 -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 偽 -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 偽 -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，

本文編號：1681002