趋化因子受体CXCR6及其配体CXCL16在膀胱尿路上皮癌中的表达及其临床意义

发布时间：2018-01-05 16:34

本文关键词：趋化因子受体CXCR6及其配体CXCL16在膀胱尿路上皮癌中的表达及其临床意义　出处：《川北医学院》2015年硕士论文　论文类型：学位论文

【摘要】：目的:观察趋化因子受体CXCR6及其配体CXCL16在膀胱尿路上皮癌和正常膀胱粘膜组织中的表达情况,并分析其与肿瘤临床生物学行为以及复发和进展的关系。为进一步深入研究CXCR6/CXCL16影响膀胱尿路上皮癌生物学行为的机制提供线索。材料和方法:选择89例初诊为膀胱尿路上皮癌组织的标本,30例正常膀胱粘膜组织:肿瘤标本中非肌层浸润性膀胱尿路上皮癌64例,肌层浸润性癌25例;低级别尿路上皮癌32例,高级别癌57例;单发肿瘤48例,多发41例;非肌层浸润性膀胱尿路上皮癌中,随访期间出现术后首次复发38例,未复发26例;出现术后首次进展22例,未进展42例。采用ElivisonTM免疫组织化学方法,检测膀胱尿路上皮癌组织、正常膀胱粘膜组织中趋化因子受体CXCR6及其配体CXCL16的表达情况。并结合患者的临床病理因素以及非肌层浸润性膀胱癌患者的预后情况进行分析。运用SPSS13.0软件进行统计学分析,趋化因子受体CXCR6及其配体CXCL16表达水平的分析采用X2检验,膀胱尿路上皮癌中CXCR6/CXCL16表达的相关性分析采用Spearman等级相关。采用Kaplan-Meier方法计算非肌层浸润性膀胱癌患者的无复发生存率和无进展生存率,绘制生存曲线并进行Log-Rank检验。以P0.05为差异有统计学意义。结果： 1.正常膀胱粘膜组织中趋化因子受体CXCR6蛋白的表达水平为:20%(6/30),肿瘤组织中为:75.3%(67/89);正常膀胱粘膜组织中趋化因子CXCL16蛋白的表达水平为10%(3/30),肿瘤组织为73%(65/89);组间比较差异均有统计学意义(P0.001、P0.001)。趋化因子受体CXCR6及其配体CXCL16蛋白在膀胱尿路上皮癌中的表达成正相关(r=0.747、P=0.000*0.001)。2.低级别和高级别膀胱尿路上皮癌中趋化因子受体CXCR6阳性表达水平分别为56%(18/32),86%(49/57),组间比较差异有统计学意义(P0.05)。非肌层浸润性膀胱癌术后复发组与未复发组趋化因子受体CXCR6蛋白的表达水平分别为84%(32/38)和46%(12/26),组间差异有统计学意义(P0.05);术后进展组与未进展组中趋化因子受体CXCR6蛋白的表达水平分别为91%(20/22)、57%(24/42),差异有统计学意义(P0.01)。膀胱尿路上皮癌组织中趋化因子CXCL16蛋白表达与患者的性别、年龄、肿瘤大小、肿瘤数目、肿瘤的临床分期、病理级别均无关。且非肌层浸润性膀胱尿路上皮癌的术后复组与未复发组、术后进展组与未进展组比较,趋化因子CXCL16蛋白的表达表达水平均无明显差异(P0.05、P0.05)。3.Kaplan-Meier曲线和Log-Rank检验显示,非肌层浸润性膀胱尿路上皮癌患者趋化因子受体CXCR6阳性表达组和CXCR6阴性组术后无复发生存率相比较,组间差异有统计学意义(P0.05)。趋化因子受体CXCR6阳性表达组和阴性表达组术后无进展生存率比较,差异有统计学意义(P0.01)。趋化因子受体CXCR6阳性表达组的无复发生存率和无进展生存率均低于阴性组。而趋化因子CXCL16的表达情况不影响非肌层浸润性膀胱尿路上皮癌患者的术后无复发生存率和无进展生存率。(P0.05、P0.05)结论:趋化因子受体CXCR6及其配体CXCL16在膀胱尿路上皮癌中的表达水平高于正常膀胱粘膜组织。趋化因子受体CXCR6在膀胱尿路上皮癌中的表达情况与其病理级别和临床分期成正相关,并且可能影响非肌层浸润性膀胱癌患者的预后。提示CXCR6/CXCL16生物学轴可能参与了膀胱尿路上皮癌的发生、发展,并可能影响患者的预后。
[Abstract]:Objective: To observe the expression of chemokine receptor CXCR6 and its ligand CXCL16 in bladder urothelial carcinoma and normal bladder mucosa tissues, and analyze its relationship with clinical and biological behavior of the tumor recurrence and progression. Provide clues for further research on the mechanism of bladder CXCR6/CXCL16 affects the biological behavior of epithelial carcinoma. Materials and methods: 89 cases of newly diagnosed bladder urothelial carcinoma specimens, 30 cases of normal bladder mucosa: tumor specimens of non muscle invasive urothelial carcinoma of the bladder in 64 cases, muscle invasive carcinoma in 25 cases; low grade urothelial carcinoma in 32 cases, 57 cases of high grade carcinoma; 48 cases of solitary tumor multiple, 41 cases; non muscle invasive urothelial carcinoma of the bladder, the first postoperative recurrence occurred in 38 cases during the follow-up period, no recurrence in 26 cases; 22 cases of the first progress after operation, no progress in 42 cases by ElivisonTM immunohistochemical method, Detection of bladder urothelial carcinoma. The expression of chemokine receptor CXCR6 and its ligand CXCL16 in normal bladder mucosa tissue. Combined with clinical pathological factors in patients with non muscle invasive bladder cancer patients prognosis were analyzed. Statistical analysis was performed using SPSS13.0 software, the chemokine receptor CXCR6 and its ligand CXCL16 expression the level of analysis using X2 test, correlation analysis between the expression of CXCR6/CXCL16 in bladder urothelial carcinoma using Spearman rank correlation. Using Kaplan-Meier method to calculate the non muscle invasive bladder cancer patients without recurrence and progression free survival, survival curve and Log-Rank test in P0.05. The difference was statistically significant. Results: 1. normal bladder tissue expression of chemokine receptor CXCR6 protein was 20% (6/30), tumor tissue was 75.3% (67/89); normal bladder Bladder mucosa in expression of chemokine CXCL16 protein 10% (3/30), the tumor tissue was 73% (65/89); there were significant differences among the groups (P0.001, P0.001). The expression of chemokine receptor CXCR6 and its ligand CXCL16 protein in bladder urothelial carcinoma was positively correlated (r=0.747, P=0.000*0.001) chemokine receptor CXCR6 expression levels were 56%.2. low grade and high grade bladder urothelial carcinoma (18/32), 86% (49/57), there were significant differences between the groups (P0.05). Non muscle invasive bladder cancer recurrence group and non recurrence group expression level factor receptor CXCR6 protein were 84% (32/38) and 46% (12/26), there was significant difference between the groups (P0.05); after the operation in group and non progressive group in the expression of chemokine receptor CXCR6 protein were 91% (20/22), 57% (24/42), the difference was statistically significant (P0.01) wings. CXCL16 gene protein expression and patient's sex, age, tumor size, tumor number, more bladder urothelial carcinoma, tumor clinical staging, pathological grade were unrelated. And non muscle invasive bladder cancer postoperative rehabilitation group and non recurrence group, comparison group and no postoperative progress in the control group, there were no significant difference between the expression of chemokine CXCL16 expression (P0.05, P0.05).3.Kaplan-Meier curve and Log-Rank test showed that non muscle invasive bladder cancer patients tend to relapse free survival compared with receptors of CXCR6 positive group and CXCR6 negative group, the two groups had statistical significance the difference between (P0.05). Chemokine receptor CXCR6 positive expression group and negative group postoperative progression free survival rate comparison, the difference was statistically significant (P0.01). Chemokine receptor CXCR6 positive expression of the relapse free survival and progression free The survival rate was lower than the negative group. The expression of chemokines CXCL16 does not affect the non muscle invasive bladder cancer patients had no recurrence and progression free survival (P0.05, P0.05). Conclusion: the expression of chemokine receptor CXCR6 and its ligand CXCL16 in bladder urothelial carcinoma higher than that in the normal bladder mucosa. The expression of chemokines and pathological grades and clinical chemokine receptor CXCR6 in bladder urothelial carcinoma staging was positively correlated, and may affect non muscle invasive bladder cancer prognosis. CXCR6/CXCL16 biological axis may be involved in bladder urothelial cancer occurrence, development. And may affect the prognosis of patients.

【学位授予单位】：川北医学院
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R737.14

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