膀胱癌组织细丝蛋白C的表达与临床病理特征及生存预后的关系

Relationship of filamin C expression in bladder cancer tissues with the clinicopathological features and prognosis of the disease

目的探讨膀胱癌组织细丝蛋白C(FLNC)的表达水平与膀胱癌患者临床病理特征及生存预后的关系。方法回顾性队列研究。纳入2013年9月—2018年9月蚌埠医科大学第一附属医院泌尿外科行根治性全膀胱切除术的膀胱癌患者55例, 其中男43例、女12例, 年龄65(56.5, 68.0)岁。对膀胱癌组织及癌旁组织行免疫组织化学染色检查及评分。观察指标:(1)观察FLNC在癌组织和癌旁组织中的表达情况;按照膀胱癌组织中FLNC免疫组织化学染色评分结果中位数, 将患者分为FLNC低表达组和FLNC高表达组, 观察分析FLNC表达水平与膀胱癌患者临床病理特征的关系;(2)纳入患者性别、年龄、肿瘤分化级别、肿瘤大小、T分期、N分期、美国癌症联合委员会(AJCC)分期和FLNC表达水平等临床病理特征进行单因素、多因素Cox比例风险回归模型分析;(3)采用Kaplan-Meier生存曲线计算临床患者累积生存率;(5)绘制受试者操作特征(ROC)曲线分析FLNC的检测对膀胱癌患者生存预后的预测价值。结果 (1)膀胱癌组织中FLNC免疫组织化学染色评分为2(2, 4)分, 高于癌旁组织的2(1, 3)分, 差异有统计学意义(Z=2.20, P=0.028)。(2)55例患者膀胱癌组织中FLNC免疫组织化学染色评分结果中位数为2分, 其中29例纳入FLNC低表达组(≤2分), 26例纳入FLNC高表达组(>2分)。FLNC低表达组T分期中T1~2期、T3~4期患者占比和AJCC分期中Ⅰ~Ⅱ期、Ⅲ~Ⅳ期患者占比分别为69.0%(20/29)、31.0%(9/29)和58.6%(17/29)、41.4%(12/29), FLNC高表达组分别为38.5%(10/26)、61.5%(16/26)和26.9%(7/26)、73.1%(19/26), 2组比较差异均有统计学意义(χ^(2)=5.15、5.60, P值均<0.05)。(3)单因素Cox比例风险回归分析结果表明, N分期、AJCC分期、FLNC表达水平是膀胱癌预后的影响因素[HR(95%CI)分别为4.345(1.724~10.948)、2.946(1.057~8.213)、3.991(1.492~11.147)]。多因素Cox比例风险回归模型分析结果表明, N分期、FLNC表达水平是膀胱癌生存预后的独立危险因素[HR(95%CI)分别为3.227(1.108~9.394)、3.409(1.198~9.700)]。(4)全组55例膀胱癌患者5年累积生存率为61.90%, 其中FLNC低表达组患者5年累积生存率为81.40%, 高于FLNC高表达组的40.60%, 2组比较差异有统计学意义(χ^(2)=8.11, P=0.004)。(5)ROC曲线结果表明, 曲线下面积(95%CI)为0.702(0.555~0.848), 约登指数为0.40, 灵敏度为0.74, 特异度为0.67, 预测价值较好。结论与癌旁组织比较, FLNC在膀胱癌组织中表达增高, 且其表达水平与肿瘤的T分期、AJCC分期有关;对于膀胱癌患者, FLNC高表达提示其生存预后不良。

Objective This study aimed to investigate the expression level of filamin C(FLNC)protein in bladder cancer tissues and its relationship with the clinicopathological characteristics and prognosis of the disease.Methods This was a retrospective cohort study.A total of 55 patients with bladder cancer who underwent radical cystectomy in the Department of Urology at the First Affiliated Hospital of Bengbu Medical University from September 2013 to September 2018 were included in this study,including 43 males and 12 females with age of 65(56.5,68.0)years.Bladder cancer and adjacent tissues were immunohistochemically stained and scored.Outcome measures included:(1)The patients were divided into the low expression group of FLNC and high expression group of FLNC in accordance with the median IHC staining score.The relationship between FLNC expression and the clinicopathological characteristics of the patients was analyzed.(2)The clinicopathological features such as sex,age,the level of tumor differentiation,tumor size,T stage,N stage,American Joint Committee on Cancer(AJCC)stage and the expression level of FLNC were included in univariate and multivariate analysis using Cox proportional hazard regression model.(3)The cumulative survival rate of clinical patients was calculated using the Kaplan-Meier method.(4)A receiver operating characteristic(ROC)curve was plotted to analyze the value of FLNC detection in the prognosis of patients with bladder cancer.Results(1)To observe the expression of FLNC in cancer tissues and adjacent tissues.The IHC staining intensity score for FLNC in bladder cancer tissues was 2(2,4),which is significantly higher than that in adjacent tissues(2[1,3],Z=2.201,P=0.028).(2)These patients were divided into two groups using the median immunohistochemical staining score(2 points)as a cutoff value,there were 29 patients in the low expression group of FLNC(≤2 points)and 26 patients in the high expression group of FLNC protein(>2 points).The proportions of patients with T1-2 and T3-4 stage diseases were 69.0%(20/29)and 31.0%(9/29)in the low FLNC group and 38.5%(10/26)and 61.5%(16/26)in the high FLNC group,and the proportions of patients with AJCCⅠ-ⅡandⅢ-Ⅳstage disease were 58.6%(17/29)and 41.4%(12/29)in the low FLNC group and 26.9%(7/26)and 73.1%(19/26)in the high FLNC group,with statistically significant differences between the two groups(χ^(2)=5.15、5.60,all P values<0.05).(3)The results of univariate Cox proportional hazard regression analysis indicated that the N stage,AJCC stage,and the expression level of FLNC were the prognostic factors of bladder cancer(HR 4.34595%CI[1.724-10.948],2.946[1.057-8.213],3.991[1.492-11.147],respectively).Multivariate Cox proportional hazard regression model analysis showed that the N stage and the expression level of FLNC were independent risk factors for the prognosis of bladder cancer[3.227(1.108-9.394)and 3.409(1.198-9.700)].(4)The 5-year cumulative survival rate of 55 patients with bladder cancer was 61.90%,and the 5-year cumulative survival rate of patients with a low FLNC expression level was 81.40%,which was higher than that of patients with a high FLNC expression level(40.60%),and the difference was statistically significant between the two groups(χ^(2)=8.11,P=0.004).(5)Based on the ROC curve results,area under the curve(95%CI)was 0.702(0.555-0.848),the Youden index was 0.40,sensitivity was 0.74,specificity was 0.67,and the predictive value was good.Conclusion The expression level of FLNC increases in bladder cancer tissues and is related to the T stage and AJCC stage.Highly expressed FLNC indicates the poor prognosis of patients.