乙肝病毒X蛋白结合蛋白过表达对膀胱癌侵袭转移及预后预测价值

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目的乙肝病毒X蛋白结合蛋白(hepatitis BX-interacting protein,HBXIP)在多种肿瘤中存在过度表达,且其过表达与肿瘤的恶性进展相关。本研究旨在探讨HBXIP过表达与膀胱尿路上皮癌临床病理特征和预后的关系。方法收集延边大学医院2010-01-01-2014-12-31有完整临床病理资料,且病理检查确诊为膀胱尿路上皮癌的100例癌组织作为研究组,10例同期癌旁组织作为对照组;另取10例配对的新鲜癌组织及癌旁组织作为研究组及对照组。采用免疫组化SP方法、蛋白质印迹法和逆转录-聚合酶链反应(reverse transcription-polymerase chain reaction,RT-PCR)方法检测HBXIP的表达,分析其与肿瘤病理分级、分期等临床病理特征的关系,同时研究HBXIP表达水平与膀胱尿路上皮癌患者预后的关系。结果免疫组化结果显示,HBXIP在膀胱尿路上皮癌中的高表达率为86.0%(86/100),明显高于癌旁正常膀胱组织中的20.0%(2/10),两组比较差异有统计学意义,P=0.036;同时,肌层浸润组中HBXIP高表达率为79.3(23/29),明显高于非肌层浸润组的50.7%(36/71),两组比较差异有统计学意义,P=0.046。蛋白质印迹法检测结果显示,膀胱尿路上皮癌中HBXIP的相对表达量为0.712±0.135,明显高于癌旁正常组织(0.326±0.075),两组比较差异有统计学意义,P=0.047。RT-PCR实验结果显示,膀胱尿路上皮癌中HBXIP mRNA的表达量为5.46±0.34,明显高于癌旁正常组织(1.01±0.20),两组比较差异有统计学意义,P=0.041;HBXIP高表达率与肿瘤浸润深度(P=0.048)及淋巴结转移(P=0.036)呈正相关;HBXIP高表达患者术后复发率为42.5%(20/47),而HBXIP低表达患者术后复发率仅为15.1%(8/53),两组比较差异有统计学意义,P=0.003。影响患者生存率的单因素分析显示,HBXIP高表达组膀胱尿路上皮癌患者术后生存率明显低于HBXIP低表达组,两组比较差异有统计学意义,P=0.014;肌层浸润组(T2~T3)术后生存率明显低于非肌层浸润组(T0~T1),两组比较差异有统计学意义,P=0.023。多因素分析显示,HBXIP表达水平是膀胱尿路上皮癌患者预后独立危险因素,P=0.031。结论 HBXIP在膀胱尿路上皮癌中存在着过表达,且其过表达与膀胱尿路上皮癌患者的恶性进展相关,其过表达可以预示膀胱尿路上皮癌患者的不良预后。 Objective HBXIP is overexpressed in a variety of tumors and its overexpression is associated with the malignant progression of the tumor. This study aimed to investigate the relationship between HBXIP overexpression and clinicopathological features and prognosis of bladder urothelial carcinoma. Methods The clinical data of 100 cases of bladder urothelial carcinoma diagnosed by pathology were collected from the Yanbian University Hospital as the research group and 10 cases of paracancerous tissues as the control group ; Another 10 cases of fresh cancer tissues and adjacent tissues as research group and control group. The expression of HBXIP was detected by immunohistochemical SP method, Western blotting and reverse transcription-polymerase chain reaction (RT-PCR), and its relationship with clinicopathological features , And to study the relationship between the expression of HBXIP and the prognosis of bladder urothelial carcinoma patients. Results The immunohistochemical results showed that the high expression rate of HBXIP in bladder urothelial carcinoma was 86.0% (86/100), which was significantly higher than that in normal adjacent normal tissues (20.0%, 2/10) (P = 0.036). Meanwhile, the high expression rate of HBXIP in myometrial invasion group was 79.3 (23/29), which was significantly higher than that in non-myometrial invasion group (50.7%, 36/71). There was significant difference between the two groups Statistical significance, P = 0.046. The results of Western blotting showed that the relative expression of HBXIP in bladder urothelial carcinoma was 0.712 ± 0.135, which was significantly higher than that in normal tissues (0.326 ± 0.075). The difference between the two groups was statistically significant (P = 0.047). The results of RT-PCR showed that the expression of HBXIP mRNA in bladder urothelial carcinoma was 5.46 ± 0.34, which was significantly higher than that in the adjacent normal tissue (1.01 ± 0.20), the difference was statistically significant (P = 0.041); HBXIP The high expression rate was positively correlated with the depth of tumor invasion (P = 0.048) and lymph node metastasis (P = 0.036). The recurrence rate was 42.5% (20/47) in patients with HBXIP overexpression, while the recurrence rate in HBXIP patients with low expression only 15.1% (8/53), the difference between the two groups was statistically significant, P = 0.003. Univariate analysis of the patients survival rate showed that the HBXIP high expression group of bladder urothelial carcinoma patients survival rate was significantly lower than HBXIP low expression group, the difference between the two groups was statistically significant, P = 0.014; myometrial invasion group ( T2 ~ T3) postoperative survival rate was significantly lower than the non-muscle infiltration group (T0 ~ T1), the difference between the two groups was statistically significant, P = 0.023. Multivariate analysis showed that HBXIP expression was an independent risk factor for prognosis in patients with bladder urothelial carcinoma, P = 0.031. Conclusions HBXIP is overexpressed in bladder urothelial carcinoma and its overexpression is associated with the malignant progression of bladder urothelial carcinoma. The overexpression of HBXIP may predict the poor prognosis of bladder urothelial carcinoma.
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