LAPTM4B-35在膀胱癌中的表达及其临床、病理和预后意义的研究

发布时间：2018-04-19 08:51

  本文选题：LAPTM4B + 膀胱癌　； 参考：《首都医科大学》2017年硕士论文

【摘要】：目的探讨溶酶体相关四次跨膜蛋白质B-35(LAPTM4B-35)在恶性膀胱组织中的表达情况及其临床病理和预后的意义。方法选取我院泌尿外科102例膀胱癌手术后石蜡标本(其中10例对应有新鲜切除组织)以及10例正常膀胱粘膜石蜡标本(10例均对应有新鲜切除组织)用于本研究。免疫印迹法:使用可以识别LAPTM4B-35的LAPTM4B-N1-99抗体检测其在10例新鲜正常膀胱粘膜组织和配对10例新鲜膀胱癌组织中表达情况。以细胞骨架蛋白beta-actin表达情况作为参照,将结果分为阳性表达和阴性表达。免疫组织化学染色法:使用LAPTM4B-N1-99抗体检测LAPTM4B-35在102例膀胱癌组织及10例正常膀胱粘膜表达情况。根据染色阳性细胞占总细胞数比例及染色强度综合记分进行结果判定。统计学方法:应用SPSS19.0 for windows软件进行数据分析。LAPTM4B-35在膀胱癌组织中的表达与临床病理因素的关联性采用χ2检验。生存分析:LAPTM4B-35在膀胱癌中高表达组与低表达组生存分析选用Kaplan-Meier法统计生存情况,单因素分析使用Log-rank检验,多因素分析使用Cox风险模型。结果免疫印迹法检测LAPTM4B-35在10例膀胱癌和10例配对正常膀胱粘膜中表达情况,膀胱癌组织中9/10例LAPTM4B-35蛋白表达阳性,正常膀胱粘膜组织中均呈阴性表达。免疫组织化学染色发现LAPTM4B-35染色得分与TNM分期(UICC 2009年第七版)和病理分级(WHO 2004)密切相关(P0.001)。免疫组织化学染色发现LAPTM4B-35蛋白表达与膀胱癌淋巴转移、侵袭性及复发密切相关(P.0001)。102例进行随访的膀胱癌患者中LAPTM4B-35低表达为56例,高表达为46例。Kaplan Meier及log-rank检验分析结果显示:LAPTM4B 35的高表达与膀胱癌患者无进展生存时间(DFS)和总体生存时间(OS)比较均有统计学意义;Cox风险模型分析表明LAPTM4B-35表达在无进展生存(RR:20.631,[95%可信区间,5.574-76.361],P.0001)和总体生存(RR:6.439,[95%可信区间,2.670-15.531],P.0001)上是晚期膀胱癌的独立预后因素。结论1、LAPTM4B-35蛋白在大多数膀胱癌患者中高表达。2、LAPTM4B-35表达与膀胱癌病理分级、临床分期、侵袭、转移及复发密切相关。3、LAPTM4B-35高表达与膀胱癌的进展和不良预后密切相关,因此有可能作为新的分子标志物用于判断膀胱癌患者预后情况。
[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.
【学位授予单位】：首都医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R737.14

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