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目的:检测沉默信息调节因子1(SIRT1)在膀胱尿路上皮癌(BUC)中的表达,并探讨其与临床病理指标的相关性。方法:选取经临床病理诊断的BUC标本72例,其中低级别尿路上皮癌42例,高级别尿路上皮癌30例;阴性对照组为正常膀胱组织19例(膀胱镜检术或膀胱切开取石术中随机取活检时取得)。应用免疫组化方法(二步法)检测SIRT1分别在低级别与高级别BUC中的表达与分布,分析其与肿瘤的分期和病理分级的关系。结果:SIRT1在正常膀胱组织和膀胱癌组织中均有表达,正常膀胱组织中阳性表达率为31.58%(6/19),而在BUC组中,阳性表达率为77.78%(56/72),明显高于正常膀胱组织(P<0.05);并且随着肿瘤分期和癌理分级的升高SIRT1蛋白的表达增加,其中低级别膀胱癌阳性表达率为69.05%(29/42),高级别膀胱癌阳性表达率为90.00%(27/30),两者间的差异具有统计学意义(P<0.05)。结论:SIRT1在BUC中高表达,可能与BUC的发生、病理分级和临床分期有关,并有可能作为判断BUC侵袭力、监测复发的肿瘤标志物。阻断SIRT1表达有望成为膀胱癌靶向治疗的新靶点。
OBJECTIVE: To detect the expression of SIRT1 in bladder urothelial carcinoma (BUC) and to investigate its relationship with clinicopathological parameters. Methods: Seventy-two BUC specimens diagnosed clinically and pathologically were selected, including 42 cases of low grade urothelial carcinoma and 30 cases of high grade urothelial carcinoma. Negative control group consisted of 19 cases of normal bladder tissue (cystoscopy or cystectomy Stone surgery randomized biopsy obtained). The expression and distribution of SIRT1 in low-grade and high-grade BUC were detected by immunohistochemistry (two-step method), and the relationship between SIRT1 expression and tumor stage and pathological grade was analyzed. Results: The positive rate of SIRT1 expression in normal bladder tissue and bladder cancer tissues was 31.58% (6/19), while in the BUC group, the positive rate was 77.78% (56/72) (P <0.05). The expression of SIRT1 protein was increased with the increase of tumor stage and cancer grade. The positive rate of low grade bladder cancer was 69.05% (29/42). The high grade bladder The positive rate of cancer was 90.00% (27/30), the difference was statistically significant (P <0.05). Conclusion: The high expression of SIRT1 in BUC may be related to the occurrence, pathological grade and clinical stage of BUC, and may be used as a tumor marker to detect the invasiveness of BUC and monitor recurrence. Blocking the expression of SIRT1 is expected to become a new target of targeted therapy of bladder cancer.