發(fā)布時間：2018-02-28 11:15

  本文關(guān)鍵詞： 喉鱗狀細(xì)胞癌 免疫組化 腫瘤血管生成 微血管密度 轉(zhuǎn)移 復(fù)發(fā) 預(yù)后 CD105 Galectin-3 EphA2 EphrinA1　出處：《廣州醫(yī)學(xué)院》2011年碩士論文　論文類型：學(xué)位論文

【摘要】：目的 喉癌的發(fā)病率有逐年增加的趨勢。關(guān)于喉癌發(fā)病相關(guān)因素的深入探究,以期早期發(fā)現(xiàn)、準(zhǔn)確診斷、良好治療,一直是研究追求的目標(biāo)。 近年來不少研究表明,惡性腫瘤的生長、轉(zhuǎn)移呈血管依賴性,新生血管不但為惡性腫瘤的生長提供了充足的養(yǎng)分、排泄代謝廢物,還為腫瘤細(xì)胞的轉(zhuǎn)移提供了良好的通道。腫瘤血管的生成在惡性腫瘤的發(fā)生、發(fā)展、侵襲、轉(zhuǎn)移及復(fù)發(fā)中,起著重要的作用。CD105、Galectin-3、EphA2和其配體EphrinA1蛋白等參與腫瘤內(nèi)血管生成,在惡性腫瘤的生物學(xué)行為中起作用。但關(guān)于這些因素在喉癌中作用的研究,還不多見。 本課題探討CD105、Galectin-3、EphA2和其配體EphrinA1蛋白在喉癌發(fā)病機制中的作用、病理學(xué)價值、在喉癌的診斷、治療、預(yù)后中的應(yīng)用意義,并為喉癌抗血管生成治療提供實驗依據(jù)。 方法 標(biāo)本均來自廣州醫(yī)學(xué)院附屬廣州市第一人民醫(yī)院耳鼻咽喉科2000年1月至2004年6月期間,住院手術(shù)患者的常規(guī)石蠟包埋組織。本課題從分子水平,應(yīng)用CD105單克隆抗體、Galectin-3單克隆抗體、EphA2多克隆抗體及EphrinA1多克隆抗體,采用免疫組化技術(shù),檢測CD105、Galectin-3、EphA2、EphrinA1蛋白在喉癌組織中的表達(dá),計算CD105標(biāo)染的微血管密度(MVD),分析該四種蛋白之間的相關(guān)性、對生存的影響。應(yīng)用SPSS統(tǒng)計軟件包(17.0)對各項結(jié)果進行統(tǒng)計學(xué)分析。 結(jié)果 1 76例喉癌組織中以CD105標(biāo)記的MVD為10.33±2.29,25例喉正常粘膜中MVD為1.20±1.04,兩組比較,其差異有顯著性意義(P0.05)。CD105-MVD的表達(dá)差異與喉癌的組織學(xué)分級、T分期、臨床分期、頸淋巴結(jié)轉(zhuǎn)移有關(guān)(P0.05);腫瘤復(fù)發(fā)與MVD有明顯相關(guān)性,MVD與預(yù)后相關(guān)。 2 Galectin-3蛋白表達(dá)的陽性率在喉癌組織中為86.84%(66/76),在喉正常粘膜中為36%(9/25),其差異有顯著性意義(P0.05)。Galectin-3蛋白表達(dá)與喉癌的T分期、臨床分期、頸淋巴結(jié)轉(zhuǎn)移有關(guān)(P0.05);腫瘤復(fù)發(fā)與Galectin-3有明顯相關(guān)性,Galectin-3與預(yù)后相關(guān)。 3 EphA2、EphrinA1表達(dá)于腫瘤細(xì)胞的細(xì)胞漿/胞膜,其陽性率分別為78.95%(60/76)、81.85%(62/76),喉正常粘膜中的陽性表達(dá)率分別為40%(10/25)、44%(11/25),其差異有顯著性意義(P0.05)。EphA2蛋白表達(dá)與腫瘤部位、組織學(xué)分級、T分期、臨床分期、淋巴結(jié)轉(zhuǎn)移有關(guān)。EphrinA1蛋白表達(dá)與腫瘤T分期、臨床分期、頸淋巴結(jié)轉(zhuǎn)移有關(guān)(P0.05),腫瘤復(fù)發(fā)與EphA2、EphrinA1有明顯相關(guān)性,EphA2、EphrinA1與預(yù)后相關(guān)。 4 CD105、Galectin-3、EphA2和EphrinA1蛋白四者兩兩之間,均呈明顯的正相關(guān)。 5生存分析顯示喉癌患者總生存期隨著CD105微血管計數(shù)的增高和Galectin-3、EphA2和EphrinA1染色級別的增高,而逐漸下降,其差異有顯著性(P0.05)。Cox Regression綜合生存分析顯示,CD105、Galectin-3、EphA2同生存期相關(guān),腫瘤分型、淋巴結(jié)轉(zhuǎn)移、TNM分期、有無復(fù)發(fā)是患者預(yù)后獨立的影響因素。 結(jié)論 1 CD105與腫瘤活性血管生成有密切聯(lián)系,是腫瘤新生血管的標(biāo)志;腫瘤血管生成有利于腫瘤的侵襲、轉(zhuǎn)移或復(fù)發(fā)。 2 Galectin-3的高表達(dá)與喉癌的發(fā)生密切相關(guān),Galectin-3在喉腫瘤血管新生、喉癌的浸潤、轉(zhuǎn)移、預(yù)后中起作用。 3 EphA2、EphrinA1在喉癌中呈高表達(dá);EphA2蛋白高表達(dá)與腫瘤部位、組織學(xué)分級、T分期、臨床分期、淋巴結(jié)轉(zhuǎn)移有關(guān);EphrinA1蛋白的高表達(dá)與腫瘤T分期、臨床分期、頸淋巴結(jié)轉(zhuǎn)移有關(guān);EphA2與EphrinA1的表達(dá)呈正相關(guān),EphrinA1蛋白表達(dá)隨著EphA2蛋白表達(dá)的增大而增大;EphA2、EphrinA1可能在喉癌的發(fā)生發(fā)展中起促進作用;EphA2、EphrinA1的高表達(dá)還可能提示了喉癌的惡性程度。 4喉癌中CD105、Galectin-3、EphA2和EphrinA1蛋白四者兩兩之間,均呈正相關(guān),四者的協(xié)同作用促進了喉癌的發(fā)生、發(fā)展。 5生存分析顯示CD105、Galectin-3、EphA2和EphrinA1蛋白的高表達(dá)與喉癌患者的生存較差有關(guān),提示四者具有潛在的預(yù)后價值。 6對CD105標(biāo)記的MVD、Galectin-3、EphA2及EphrinA1的檢測,有助于喉癌的診斷;可作為判斷喉癌侵襲、轉(zhuǎn)移及預(yù)后的指標(biāo);并為喉癌的抗血管生成基因治療提供實驗依據(jù)。
[Abstract]:Purpose The incidence of laryngeal cancer has been increasing year by year . In order to find out early , accurate diagnosis and good treatment , it has been the goal of research . Tumor angiogenesis plays an important role in the development , development , invasion , metastasis and recurrence of malignant tumor . CD105 , Galectin - 3 , EphA2 and its ligand EphrinA1 protein play an important role in the development , invasion , metastasis and recurrence of malignant tumors . The purpose of this study was to investigate the role of CD105 , Galectin - 3 , EphA2 and its ligand EphrinA1 in the pathogenesis of laryngeal cancer . method The expression of CD105 , Galectin - 3 , EphA2 , EphA2 polyclonal antibody and EphrinA1 polyclonal antibody were detected by immunohistochemistry . The correlation between CD105 , Galectin - 3 , EphA2 and EphrinA1 in laryngeal cancer tissues was analyzed . Results The MVD of CD105 - MVD was 10.33 鹵 2.29 , MVD was 1.20 鹵 1.04 in 25 normal mucosa ( P0.05 ) . The expression of CD105 - MVD was correlated with histological grade , T stage , clinical stage and cervical lymph node metastasis ( P0.05 ) . The expression of Galectin - 3 protein was 86.84 % ( 66 / 76 ) in laryngeal carcinoma and 36 % ( 9 / 25 ) in normal mucosa . The expression of Galectin - 3 was related to T stage , clinical stage and cervical lymph node metastasis ( P0.05 ) . EphA2 and EphrinA1 were expressed in tumor cells . The positive rates were 78.95 % ( 60 / 76 ) , 81.85 % ( 62 / 76 ) , 40 % ( 10 / 25 ) and 44 % ( 11 / 25 ) respectively . EphA2 protein expression was related to tumor site , histological grade , T stage , clinical stage and lymph node metastasis . 4 CD105 , Galectin - 3 , EphA2 and EphrinA1 were positively correlated . Survival analysis showed that the overall survival time of patients with laryngeal cancer increased with the increase of CD105 microvessels counts and the increase of Galectin - 3 , EphA2 and EphrinA1 staining levels , and the difference was significant ( P0.05 ) . Cox regression analysis showed that CD105 , Galectin - 3 , EphA2 were related to survival , tumor typing , lymph node metastasis , TNM staging , and whether recurrence was an independent prognostic factor . Conclusion 1 CD105 is closely related to the angiogenesis of tumor , which is the marker of tumor neovascularization ; tumor angiogenesis is beneficial to invasion , metastasis or recurrence of tumor . The high expression of Galectin - 3 is closely related to the occurrence of laryngeal cancer , and Galectin - 3 plays a role in the invasion , metastasis and prognosis of laryngeal tumor angiogenesis and laryngeal carcinoma . EphA2 and EphrinA1 are related to the expression of EphA2 and EphrinA1 . EphA2 and EphrinA1 may play a role in the development of laryngeal cancer ; EphA2 , EphrinA1 may also promote the malignancy of laryngeal cancer . There were positive correlation between CD105 , Galectin - 3 , EphA2 and EphrinA1 protein in laryngeal carcinoma . 5 Survival analysis showed that high expression of CD105 , Galectin - 3 , EphA2 and EphrinA1 was associated with poor survival in patients with laryngeal cancer , suggesting that four patients had a potential prognostic value . 6 The detection of MVD , Galectin - 3 , EphA2 and EphrinA1 marked by CD105 can help the diagnosis of laryngeal cancer . It can be used as an index to judge the invasion , metastasis and prognosis of laryngeal cancer . It can provide experimental basis for the anti - angiogenic gene therapy of laryngeal cancer .

【學(xué)位授予單位】：廣州醫(yī)學(xué)院
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2011
【分類號】：R739.65

【參考文獻】

相關(guān)期刊論文 前8條

1 石菲;彭貴勇;孫永剛;姚大鵬;;Galectin-3在食管鱗癌中的表達(dá)及其臨床意義[J];第三軍醫(yī)大學(xué)學(xué)報;2008年11期

2 楊蕾;陳文寬;曾宗淵;郭朱明;;喉癌聲門上型微血管生成及其臨床意義[J];中國耳鼻咽喉頭頸外科;2009年03期

3 姚衛(wèi)東,姜惠峰,曲桂梅,于文方,王威,姜蕾,潘旭波,郝俊梅;肝細(xì)胞癌組織中endoglin(CD_(105))和VEGF及p57~(kip2)表達(dá)與預(yù)后的關(guān)系[J];腫瘤防治雜志;2005年05期

4 許良中，楊文濤;免疫組織化學(xué)反應(yīng)結(jié)果的判斷標(biāo)準(zhǔn)[J];中國癌癥雜志;1996年04期

5 劉輝;郭建文;劉江惠;左連富;;EphA2/EphrinA1在胃癌中的表達(dá)及其意義[J];中國腫瘤臨床;2008年10期

6 杜強;季文樾;關(guān)超;許青云;;手術(shù)切除治療喉癌的預(yù)后分析[J];中華腫瘤雜志;2006年03期

7 駱成玉;腫瘤血管生成對微轉(zhuǎn)移影響的研究進展[J];中國普外基礎(chǔ)與臨床雜志;2003年05期

8 姚永忠;潘一明;孫喜太;仇毓東;丁義濤;;血管新生過程中CD105的表達(dá)變化及其作用[J];中國普外基礎(chǔ)與臨床雜志;2009年10期

，

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