ING4、P53、Ki-67、Fas及FasL在膀胱尿路上皮癌中的表达及临床意义
发布时间：2018-08-28 07:42
【摘要】：目的:通过检测ING4、P53、Ki-67、Fas/Fas L在膀胱尿路上皮癌中的表达变化,探讨ING4、P53、Ki-67、Fas/Fas L在膀胱尿路上皮癌发生发展中的作用和临床意义,分析ING4与P53、Ki-67、Fas/Fas L之间的相互关系,并对膀胱癌的标记物、基因治疗、早期诊断、术后随访及预后判断提供一定的理论基础。方法:收集川北医学院附属医院和南充市中心医院2014~2015年经手术切除的并有完整临床资料的膀胱尿路上皮癌标本60例,癌旁组织60例,膀胱正常黏膜组织37例。采用免疫组织化学Elivsion TMPlus二步法检测ING4、P53、Ki-67、Fas及Fas L在膀胱尿路上皮癌、癌旁组织及膀胱正常黏膜组织中的表达。结果:1.ING4在膀胱尿路上皮癌的阳性表达率70%(42/60),在癌旁组织的阳性表达率100%(60/60),在正常膀胱黏膜组织中的阳性表达率97.2%(36/37),膀胱尿路上皮癌的阳性表达率低于膀胱正常黏膜组织和癌旁组织,差异有统计学意义(P0.05),正常膀胱黏膜组织与癌旁组织的阳性表达率差异无统计学意义(P0.05)。随着病理级别的分化程度或临床分期的增高,ING4在膀胱尿路上皮癌中的表达呈下降趋势(P0.05)。2.P53在膀胱尿路上皮癌的阳性表达率96.7%(58/60),在癌旁组织中的阳性表达率13.3%(8/60),在膀胱正常黏膜组织中的阳性表达率中13.5%(5/37),膀胱尿路上皮癌的阳性表达率高于膀胱正常黏膜组织和癌旁组织(P0.05),膀胱正常黏膜组织与癌旁组织的阳性表达率差异无统计学意义(P0.05)。随着病理级别的分化程度或临床分期增高,P53在膀胱尿路上皮癌中的表达呈上升趋势(P0.05)。P53在多发的膀胱尿路上皮癌的的阳性表达率高于单发的膀胱尿路上皮癌(P0.05)。3.Ki-67在膀胱尿路上皮癌的阳性表达率91.7%(55/60),在癌旁组织中的阳性表达率11.7%(7/60),在膀胱正常黏膜组织中的阳性表达率2.7%(1/37),膀胱尿路上皮癌的阳性表达率高于膀胱正常黏膜组织和癌旁组织(P0.05),膀胱正常黏膜组织与癌旁组织的阳性表达率差异无统计学意义(P0.05)。随着病理级别的分化程度或临床分期增高,Ki-67在膀胱尿路上皮癌中的表达呈上升趋势(P0.05),Ki-67在多发的膀胱尿路上皮癌的的阳性表达率高于单发的膀胱尿路上皮癌(P0.05)。4.Fas在膀胱尿路上皮癌的阳性表达率70%(42/60),在癌旁组织中的阳性表达率88.3%(53/60),在膀胱正常黏膜组织中的阳性表达率89.2%(34/37),膀胱正常黏膜组织和癌旁组织的阳性表达率高于膀胱尿路上皮癌(P0.05),膀胱正常黏膜组织与癌旁组织的阳性表达率差异无统计学意义(P0.05)。随着病理级别增高,Fas在膀胱尿路上皮癌中的表达呈下降趋势(P0.05)。5.Fas L在膀胱尿路上皮癌的阳性表达率76.7%(46/60),在癌旁组织中的阳性表达率100%(60/60),在膀胱正常黏膜组织中的阳性表达率94.6%(35/37),膀胱尿路上皮癌的阳性表达率低于膀胱正常黏膜组织和癌旁组织(P0.05),膀胱正常黏膜组织与癌旁的阳性表达率差异无统计学意义(P0.05)。6.应用Spearman等级相关性分析ING4与P53、Ki-67、Fas/Fas L之间的关系。ING4与P53、Ki-67呈负相关,ING4与Fas/Fas L呈正相关,相关性具有统计学意义(P0.05)。结论:1.ING4在膀胱尿路上皮癌中的低表达或缺失,提示ING4在膀胱尿路上皮癌中起抑制作用。随着膀胱癌的临床分期或病理分级增高呈下降趋势,提示ING4与肿瘤的侵袭性存在紧密的关系,说明ING4可成为预测膀胱肿瘤进展的相对可靠的临床指标之一。2.P53在膀胱尿路上皮癌中的高表达,并随着膀胱癌的临床分期或病理分级及肿瘤个数增高呈上升趋势,提示P53蛋白的过度表达是膀胱癌高度恶性的标志之一。3.Ki-67在膀胱尿路上皮癌中的高表达,并随着膀胱尿路上皮癌的临床分期或病理分级及肿瘤个数增高呈上升趋势,提示Ki-67可以成为膀胱癌发生发展、诊断及预后的良好指标之一,并对预测膀胱癌的早期复发、恶化及治疗效果的判定有重要的临床意义。4.Fas在膀胱尿路上皮癌中的低表达及缺失,提示膀胱肿瘤可抵制由Fas介导的凋亡途径从而对肿瘤进展产生重要的影响。因此检测Fas的缺失可成为决定哪些病人更加需要进一步治疗方案的参考因素之一。5.Fas L在膀胱尿路上皮癌中的阳性表达率低于在良性病变,提示其膀胱肿瘤在由良性病变转变为恶性病变形成过程中扮演着重要的作用,并在膀胱肿瘤已形成恶变形成后,不随细胞分化程度、生长情况而改变。但Fas L在正常组织中的阳性表达高于癌组织,则需要进一步研究。6.ING4与P53、Ki-67呈正相关,与Fas/Fas L呈负相关,提示膀胱肿瘤的发生和进展是由多种因素、多个基因共同参与的一个较为复杂的演变过程,联合检测多个生物学指标可能对膀胱癌的标记物、早期诊断、精准治疗、术后随访及预后判断提供一定的帮助。
[Abstract]:Objective: To investigate the role and clinical significance of ING4, P53, Ki-67, Fas/Fas L in the development of bladder urothelial carcinoma by detecting the expression of ING4, P53, Ki-67, Fas/Fas L in bladder urothelial carcinoma, and to analyze the relationship between ING4, P53, Ki-67, Fas/Fas L, and the markers, gene therapy, early diagnosis of bladder cancer. Methods: From 2014 to 2015, 60 specimens of bladder urothelial carcinoma, 60 adjacent tissues and 37 normal bladder mucosa were collected from the Affiliated Hospital of North Sichuan Medical College and Nanchong Central Hospital with complete clinical data. The expression of ING4, P53, Ki-67, Fas and Fas L in bladder urothelial carcinoma, adjacent tissues and normal bladder mucosa were detected. Results: 1. The positive expression rate of ING4 in bladder urothelial carcinoma was 70% (42/60), 100% (60/60) in adjacent tissues, 97.2% (36/37) in normal bladder mucosa, and 97.2% (36/37) in bladder urothelial carcinoma. The positive expression rate of ING4 in bladder urothelial carcinoma was significantly lower than that in normal bladder mucosa and adjacent tissues (P 0.05). There was no significant difference between normal bladder mucosa and adjacent tissues (P 0.05). The positive expression rate of P53 in bladder urothelial carcinoma was 96.7% (58/60), 13.3% (8/60) in paracancerous tissue, 13.5% (5/37) in normal bladder mucosa, and higher than that in normal bladder mucosa and paracancerous tissue (P 0.05). The positive expression rate of P53 in bladder urothelial carcinoma was higher than that in single bladder urothelial carcinoma (P 0.05). 3. Ki-67 in bladder urothelial carcinoma (P 0.05). The positive expression rate of urothelial carcinoma was 91.7% (55/60), 11.7% (7/60) in paracancerous tissues, 2.7% (1/37) in normal bladder mucosa, higher than that in normal bladder mucosa and paracancerous tissues (P 0.05). There was no significant difference (P 0.05). The expression of Ki-67 in bladder urothelial carcinoma increased with pathological grade or clinical stage (P 0.05). The positive expression rate of Ki-67 in multiple bladder urothelial carcinoma was higher than that in single bladder urothelial carcinoma (P 0.05). 4. Fas expression in bladder urothelial carcinoma was higher than that in single bladder urothelial carcinoma (P 0.05). The positive rate was 70% (42/60), 88.3% (53/60) in the adjacent tissues, 89.2% (34/37) in the normal bladder mucosa, and higher in the normal bladder mucosa and adjacent tissues than in the bladder urothelial carcinoma (P 0.05). The positive expression rate of Fas L in bladder urothelial carcinoma was 76.7% (46/60), 100% (60/60) in adjacent tissues, 94.6% (35/37) in normal bladder mucosa and 94.6% (35/37) in bladder urothelial carcinoma. There was no significant difference between normal bladder mucosa and adjacent tissues (P 0.05). 6. Spearman grade correlation analysis was used to analyze the relationship between ING4 and P53, Ki-67, Fas/Fas L. ING4 was negatively correlated with P53, Ki-67, and ING4 was positively correlated with Fas/Fas L. Conclusion: 1. The low expression or deletion of ING4 in bladder urothelial carcinoma suggests that ING4 may play an inhibitory role in bladder urothelial carcinoma. The high expression of P53 protein in bladder urothelial carcinoma is one of the relatively reliable clinical indicators. 2. The high expression of P53 protein in bladder urothelial carcinoma increases with the clinical stage or pathological grade of bladder cancer and the increase of the number of tumors, suggesting that the overexpression of P53 protein is one of the markers of high malignancy of bladder cancer. 3. The high expression of Ki-67 in bladder urothelial carcinoma and with the increase of bladder cancer. The clinical stage or pathological grade of urothelial carcinoma and the increasing number of tumors showed an upward trend, suggesting that Ki-67 may be one of the good indicators for the occurrence, development, diagnosis and prognosis of bladder cancer, and has important clinical significance for predicting the early recurrence, deterioration and treatment effect of bladder cancer. 4. Fas in the low surface of bladder urothelial carcinoma. It is suggested that Fas-mediated apoptotic pathway can be resisted by bladder tumor and thus has an important impact on tumor progression. Therefore, the detection of Fas-deleted may be one of the reference factors in deciding which patients need further treatment. 5. The positive expression of Fas-L in bladder urothelial carcinoma is lower than that in benign lesions, suggesting that Fas-mediated apoptotic pathway may play an important role in bladder cancer progression. Bladder tumors play an important role in the process of transformation from benign to malignant lesions, and after malignant transformation of bladder tumors, they do not change with the degree of cell differentiation and growth. S/Fas L is negatively correlated, suggesting that the occurrence and progression of bladder cancer is a complicated evolutionary process involving multiple factors and genes. Combined detection of multiple biological markers may be helpful for markers, early diagnosis, accurate treatment, postoperative follow-up and prognosis judgment of bladder cancer.
【学位授予单位】：川北医学院
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R737.14
本文编号：2208739
[Abstract]:Objective: To investigate the role and clinical significance of ING4, P53, Ki-67, Fas/Fas L in the development of bladder urothelial carcinoma by detecting the expression of ING4, P53, Ki-67, Fas/Fas L in bladder urothelial carcinoma, and to analyze the relationship between ING4, P53, Ki-67, Fas/Fas L, and the markers, gene therapy, early diagnosis of bladder cancer. Methods: From 2014 to 2015, 60 specimens of bladder urothelial carcinoma, 60 adjacent tissues and 37 normal bladder mucosa were collected from the Affiliated Hospital of North Sichuan Medical College and Nanchong Central Hospital with complete clinical data. The expression of ING4, P53, Ki-67, Fas and Fas L in bladder urothelial carcinoma, adjacent tissues and normal bladder mucosa were detected. Results: 1. The positive expression rate of ING4 in bladder urothelial carcinoma was 70% (42/60), 100% (60/60) in adjacent tissues, 97.2% (36/37) in normal bladder mucosa, and 97.2% (36/37) in bladder urothelial carcinoma. The positive expression rate of ING4 in bladder urothelial carcinoma was significantly lower than that in normal bladder mucosa and adjacent tissues (P 0.05). There was no significant difference between normal bladder mucosa and adjacent tissues (P 0.05). The positive expression rate of P53 in bladder urothelial carcinoma was 96.7% (58/60), 13.3% (8/60) in paracancerous tissue, 13.5% (5/37) in normal bladder mucosa, and higher than that in normal bladder mucosa and paracancerous tissue (P 0.05). The positive expression rate of P53 in bladder urothelial carcinoma was higher than that in single bladder urothelial carcinoma (P 0.05). 3. Ki-67 in bladder urothelial carcinoma (P 0.05). The positive expression rate of urothelial carcinoma was 91.7% (55/60), 11.7% (7/60) in paracancerous tissues, 2.7% (1/37) in normal bladder mucosa, higher than that in normal bladder mucosa and paracancerous tissues (P 0.05). There was no significant difference (P 0.05). The expression of Ki-67 in bladder urothelial carcinoma increased with pathological grade or clinical stage (P 0.05). The positive expression rate of Ki-67 in multiple bladder urothelial carcinoma was higher than that in single bladder urothelial carcinoma (P 0.05). 4. Fas expression in bladder urothelial carcinoma was higher than that in single bladder urothelial carcinoma (P 0.05). The positive rate was 70% (42/60), 88.3% (53/60) in the adjacent tissues, 89.2% (34/37) in the normal bladder mucosa, and higher in the normal bladder mucosa and adjacent tissues than in the bladder urothelial carcinoma (P 0.05). The positive expression rate of Fas L in bladder urothelial carcinoma was 76.7% (46/60), 100% (60/60) in adjacent tissues, 94.6% (35/37) in normal bladder mucosa and 94.6% (35/37) in bladder urothelial carcinoma. There was no significant difference between normal bladder mucosa and adjacent tissues (P 0.05). 6. Spearman grade correlation analysis was used to analyze the relationship between ING4 and P53, Ki-67, Fas/Fas L. ING4 was negatively correlated with P53, Ki-67, and ING4 was positively correlated with Fas/Fas L. Conclusion: 1. The low expression or deletion of ING4 in bladder urothelial carcinoma suggests that ING4 may play an inhibitory role in bladder urothelial carcinoma. The high expression of P53 protein in bladder urothelial carcinoma is one of the relatively reliable clinical indicators. 2. The high expression of P53 protein in bladder urothelial carcinoma increases with the clinical stage or pathological grade of bladder cancer and the increase of the number of tumors, suggesting that the overexpression of P53 protein is one of the markers of high malignancy of bladder cancer. 3. The high expression of Ki-67 in bladder urothelial carcinoma and with the increase of bladder cancer. The clinical stage or pathological grade of urothelial carcinoma and the increasing number of tumors showed an upward trend, suggesting that Ki-67 may be one of the good indicators for the occurrence, development, diagnosis and prognosis of bladder cancer, and has important clinical significance for predicting the early recurrence, deterioration and treatment effect of bladder cancer. 4. Fas in the low surface of bladder urothelial carcinoma. It is suggested that Fas-mediated apoptotic pathway can be resisted by bladder tumor and thus has an important impact on tumor progression. Therefore, the detection of Fas-deleted may be one of the reference factors in deciding which patients need further treatment. 5. The positive expression of Fas-L in bladder urothelial carcinoma is lower than that in benign lesions, suggesting that Fas-mediated apoptotic pathway may play an important role in bladder cancer progression. Bladder tumors play an important role in the process of transformation from benign to malignant lesions, and after malignant transformation of bladder tumors, they do not change with the degree of cell differentiation and growth. S/Fas L is negatively correlated, suggesting that the occurrence and progression of bladder cancer is a complicated evolutionary process involving multiple factors and genes. Combined detection of multiple biological markers may be helpful for markers, early diagnosis, accurate treatment, postoperative follow-up and prognosis judgment of bladder cancer.
【学位授予单位】：川北医学院
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R737.14
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