细胞分裂周期相关蛋白5在肾透明细胞癌中的表达及临床意义

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目的:探讨细胞分裂周期相关蛋白5(CDCA5)基因在肾透明细胞癌(ccRCC)中的表达情况和预后意义。方法:基于肿瘤基因组图谱(TCGA)的UALCAN等多个在线数据库筛选肾透明细胞癌分级、分期和预后高度相关的差异表达基因(DEGs)。收集2012年1月至2016年8月于解放军总医院行肾癌切除术且随访超过5年的127例患者临床病理资料,用癌组织及癌旁组织蜡块标本制作组织芯片(TMA),免疫组织化学评分评估CDCA5表达高低,将其分为CDCA5低表达组(n n=77)和CDCA5高表达组(n n=50),并分析预后相关性。采用n χ2检验比较患者临床病理CDCA5表达差异,Kaplan-Meier法和Cox回归模型进行生存分析和预后影响因素分析。n 结果:组织芯片免疫组织化学显示CDCA5在ccRCC组织中高表达率为39.37%(50/127),低表达率为60.63%(77/127)。CDCA5高表达组与较大肿瘤直径(n χ2=5.550,n P<0.05)、远处转移(n χ2=13.402,n P<0.01)、高TNM分期(n χ2=19.634,n P<0.01)、高Furhman分级(n χ2=9.342,n P<0.01)有关,与年龄、性别、体重指数、术前血尿、手术入路、手术方式、有无合并慢性病等无明显相关。随访时间(72.77±15.64)个月,CDCA5高表达组5年无进展生存期(PFS)为60.00%,总生存期(OS)为90.00%;CDCA5低表达组5年PFS为88.31%,OS为90.91%,Kaplan-Meier生存分析显示CDCA5表达和Furhman分级是影响OS的独立预后因素,多因素Cox回归比例风险模型显示,CDCA5高表达量[风险比(n HR)=145.920,n P<0.01]是影响OS的危险因素,淋巴结无转移(n HR=0.010,n P<0.05)则降低对OS的影响;CDCA5高表达量(n HR=15.217,n P60岁(n HR=4.203,n P<0.05)是影响PFS的危险因素。n 结论:CDCA5表达上调是肾透明细胞癌不良预后新的分子标志物和肿瘤治疗潜在新靶点。“,”Objective:To explore relationship between cell division cycle associated 5 (CDCA5) expression and its prognostic significance in clear cell renal cell carcinoma (ccRCC) .Methods:Based on several online the cancer genome atlas (TCGA) analysis platforms like UALCAN dataset, we screen differentially expressed genes (DEGs) highly correlated with tumor grades, stages and prognostic significance in ccRCC. We retrospectively investigated 127 patients’ clinicopathological characteristics who underwent nephrectomyin Chinese PLA General Hospital from January 2012 to August 2016 with follow-ups more than 5 years. Tissue microarrays (TMA) is thus constructed by paraffin embedded blocks of tumor and adjacent normal tissues. Thereafter, immunohistochemical staining (IHC) scores were adopted to define its expression level, with low-expressed group (n n=77) and high-expressed group (n n=50) , and its correlation with prognosis. Clinicopathological characteristics of CDCA5 expression were compared by n χ2 test, thereafter Kaplan-Meier method and Cox proportional risk regression model were adopted to survival analysis and prognostic factors analysis.n Results:TMA stain demonstrated that CDCA5 high expression rate is 39.37% (50/127) while low expression rate 60.63% (77/127) . Overexpression of CDCA5 is correlated with larger tumor size (n χ2=5.550, n P<0.05) , distant metastasis (n χ2=13.402, n P<0.01) , higher TNM stage (n χ2=19.634, n P<0.01) and higher Furhman grade (n χ2=9.342, n P<0.01) but not with age, sex, BMI, hematuria, surgical approaches and chronic disease. After following up (72.77±15.64) mouths, 5-years progression-free survival in high CDCA5 expression group is 60.00% while overall survival is 90.00%; 5-years PFS in low CDCA5 expression group is 88.31% while OS is 90.91%. Kaplan-Meier survival analysis showed CDCA5 expression and Furhman grade are independent prognostic factors for OS. Cox stepwise proportional hazards analysis indicated that upregulation of CDCA5 is a poor prognostic factor [Hazard ratio (n HR)=145.920, n P<0.01] for OS, while no lymph node invasion is a good indicator (n HR=0.010, n P<0.05) . Moreover, CDCA5 expression (n HR=15.217, n P<0.01) and age more than 60 (n HR=4.203, n P<0.05) are hazards factor for PFS.n Conclusion:CDCA5 upregulation could be used as a poor prognosis factor for ccRCC and a new potential therapeutic target.
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