LAPTM4B-35在膀胱癌中的表達(dá)及其臨床、病理和預(yù)后意義的研究
本文選題:LAPTM4B + 膀胱癌; 參考:《首都醫(yī)科大學(xué)》2017年碩士論文
【摘要】:目的探討溶酶體相關(guān)四次跨膜蛋白質(zhì)B-35(LAPTM4B-35)在惡性膀胱組織中的表達(dá)情況及其臨床病理和預(yù)后的意義。方法選取我院泌尿外科102例膀胱癌手術(shù)后石蠟標(biāo)本(其中10例對應(yīng)有新鮮切除組織)以及10例正常膀胱粘膜石蠟標(biāo)本(10例均對應(yīng)有新鮮切除組織)用于本研究。免疫印跡法:使用可以識別LAPTM4B-35的LAPTM4B-N1-99抗體檢測其在10例新鮮正常膀胱粘膜組織和配對10例新鮮膀胱癌組織中表達(dá)情況。以細(xì)胞骨架蛋白beta-actin表達(dá)情況作為參照,將結(jié)果分為陽性表達(dá)和陰性表達(dá)。免疫組織化學(xué)染色法:使用LAPTM4B-N1-99抗體檢測LAPTM4B-35在102例膀胱癌組織及10例正常膀胱粘膜表達(dá)情況。根據(jù)染色陽性細(xì)胞占總細(xì)胞數(shù)比例及染色強(qiáng)度綜合記分進(jìn)行結(jié)果判定。統(tǒng)計學(xué)方法:應(yīng)用SPSS19.0 for windows軟件進(jìn)行數(shù)據(jù)分析。LAPTM4B-35在膀胱癌組織中的表達(dá)與臨床病理因素的關(guān)聯(lián)性采用χ2檢驗(yàn)。生存分析:LAPTM4B-35在膀胱癌中高表達(dá)組與低表達(dá)組生存分析選用Kaplan-Meier法統(tǒng)計生存情況,單因素分析使用Log-rank檢驗(yàn),多因素分析使用Cox風(fēng)險模型。結(jié)果免疫印跡法檢測LAPTM4B-35在10例膀胱癌和10例配對正常膀胱粘膜中表達(dá)情況,膀胱癌組織中9/10例LAPTM4B-35蛋白表達(dá)陽性,正常膀胱粘膜組織中均呈陰性表達(dá)。免疫組織化學(xué)染色發(fā)現(xiàn)LAPTM4B-35染色得分與TNM分期(UICC 2009年第七版)和病理分級(WHO 2004)密切相關(guān)(P0.001)。免疫組織化學(xué)染色發(fā)現(xiàn)LAPTM4B-35蛋白表達(dá)與膀胱癌淋巴轉(zhuǎn)移、侵襲性及復(fù)發(fā)密切相關(guān)(P.0001)。102例進(jìn)行隨訪的膀胱癌患者中LAPTM4B-35低表達(dá)為56例,高表達(dá)為46例。Kaplan Meier及l(fā)og-rank檢驗(yàn)分析結(jié)果顯示:LAPTM4B 35的高表達(dá)與膀胱癌患者無進(jìn)展生存時間(DFS)和總體生存時間(OS)比較均有統(tǒng)計學(xué)意義;Cox風(fēng)險模型分析表明LAPTM4B-35表達(dá)在無進(jìn)展生存(RR:20.631,[95%可信區(qū)間,5.574-76.361],P.0001)和總體生存(RR:6.439,[95%可信區(qū)間,2.670-15.531],P.0001)上是晚期膀胱癌的獨(dú)立預(yù)后因素。結(jié)論1、LAPTM4B-35蛋白在大多數(shù)膀胱癌患者中高表達(dá)。2、LAPTM4B-35表達(dá)與膀胱癌病理分級、臨床分期、侵襲、轉(zhuǎn)移及復(fù)發(fā)密切相關(guān)。3、LAPTM4B-35高表達(dá)與膀胱癌的進(jìn)展和不良預(yù)后密切相關(guān),因此有可能作為新的分子標(biāo)志物用于判斷膀胱癌患者預(yù)后情況。
[Abstract]:Objective to investigate the expression of lysosomal four transmembrane protein B-35 LAPTM4B-35 in malignant bladder and its clinicopathological and prognostic significance.Methods 102 postoperative paraffin specimens of bladder cancer (10 cases with fresh resected tissue) and 10 cases of normal bladder mucosa (10 cases with fresh resected tissue) were selected for this study.Western blot: the expression of LAPTM4B-35 was detected in 10 fresh normal bladder mucosa tissues and 10 matched fresh bladder cancer tissues using LAPTM4B-N1-99 antibody which could recognize LAPTM4B-35.The expression of cytoskeleton beta-actin was divided into positive expression and negative expression.Immunohistochemical staining: LAPTM4B-N1-99 antibody was used to detect the expression of LAPTM4B-35 in 102 cases of bladder cancer and 10 cases of normal bladder mucosa.The results were determined according to the proportion of positive cells to total cells and the comprehensive score of staining intensity.Methods: the correlation between the expression of LAPTM4B-35 and clinicopathological factors in bladder cancer was analyzed by SPSS19.0 for windows software. 蠂 2 test was used to analyze the correlation between the expression of LAPTM4B-35 and clinicopathological factors.Survival analysis: survival analysis of high expression group and low expression group in bladder cancer Kaplan-Meier method was used for survival analysis, Log-rank test was used for univariate analysis, and Cox risk model was used for multivariate analysis.Results the expression of LAPTM4B-35 was detected by Western blot in 10 cases of bladder cancer and 10 cases of matched normal bladder mucosa. Nine out of 10 cases of bladder cancer were positive for LAPTM4B-35 protein expression, and all cases were negative for LAPTM4B-35 expression in normal bladder mucosa.Immunohistochemical staining showed that the score of LAPTM4B-35 staining was closely related to TNM staging (seventh edition 2009) and pathological grading (P0.001).Immunohistochemical staining showed that the expression of LAPTM4B-35 protein was closely related to lymphatic metastasis, invasion and recurrence of bladder cancer. The low expression of LAPTM4B-35 was found in 56 patients with bladder cancer.The results of Meier and log-rank test showed that the high expression of LAPTM4B-35 in 46 patients with bladder cancer was significantly higher than that in patients with bladder cancer (DFS) and overall survival time (OS). The results of Cox risk model analysis showed that the expression of LAPTM4B-35 was not progressive in bladder cancer patients.RR: 631, [95% CI 5.574-76.361] P.0001 and overall survival RR: 6.439, [95% CI 2.670-15.531] P.0001) are independent prognostic factors of advanced bladder cancer.Conclusion 1 the overexpression of LAPTM4B-35 protein in most bladder cancer patients is closely related to the pathological grade, clinical stage, invasion, metastasis and recurrence of bladder cancer, and the high expression of LAPTM4B-35 protein is closely related to the progression and poor prognosis of bladder cancer.Therefore, it may be used as a new molecular marker to judge the prognosis of bladder cancer patients.
【學(xué)位授予單位】:首都醫(yī)科大學(xué)
【學(xué)位級別】:碩士
【學(xué)位授予年份】:2017
【分類號】:R737.14
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