BCL3在上皮性卵巢癌中的表达及其临床意义

Expression and clinical significance of BCL3 in epithelial ovarian cancer

目的:探究B细胞淋巴瘤因子3(BCL3)在上皮性卵巢癌(EOC)中的表达、基因改变及临床意义。方法:应用Oncomine数据库和GEPIA网站分析BCL3 mRNA在EOC中的表达水平,KM plotter数据库分析BCL3 mRNA表达水平对患者预后影响。使用cBioPortal网站探究BCL3发生基因改变、拷贝数改变(CNA)频率及对预后影响。选取80例EOC与18例正常卵巢组织标本,免疫组化(IHC)染色验证BCL3蛋白在EOC中的表达水平。结果:Oncomine数据库对7项数据集整合分析示,BCL3 mRNA在EOC中高表达(P=0.016),GEPIA分析同样证实BCL3 mRNA高表达(P<0.05)。KM plotter分析示,BCL3 mRNA高表达患者的整体生存率(OS)降低(P=0.012)。cBioPortal分析BCL3发生基因改变频率8%、CNA频率3%,均显著降低患者的OS(P分别为0.0161和6.206×10-6)。IHC证实,BCL3蛋白在EOC中显著高表达(P<0.001),细胞核蛋白表达水平与有无局部淋巴结转移(P=0.048)、腹水含量(P=0.035)及分化级别(P=0.017)相关。生存分析示,BCL3核蛋白中高表达有降低患者生存率趋势,但差异无统计学意义(P=0.394)。结论:BCL3 mRNA及蛋白均在EOC中高表达,且BCL3 mRNA高表达、BCL3发生基因改变或CNA均可降低患者OS,BCL3基因有望成为EOC患者治疗的潜在靶点。

Objective:To investigate the expression,gene alteration and its clinical significance of B-Cell CLL/Lymphoma 3(BCL3)in epithelial ovarian cancer(EOC).Methods:The Oncomine database and GEPIA website were used to analyze the expression level of BCL3 mRNA in epithelial ovarian cancer(EOC),and the effect of BCL3 mRNA expression on prognosis was analyzed by KM plotter database.The cBioPortal website was used to explore the BCL3 gene alteration,copy number alteration(CNA)frequency and its effect on prognosis.Immunohistochemistry(IHC)was performed on 80 EOC and 18 normal ovarian tissues to verify the expression level of BCL3 protein.Result:The integration analysis of 7 datasets in Oncomine database showed that BCL3 mRNA was highly expressed in EOC(P=0.016),and GEPIA analysis also confirmed that BCL3 mRNA was highly expressed(P<0.05).KM plotter analysis showed that overall survival(OS)was decreased in patients with high BCL3 mRNA expression(P=0.012).CBioPortal analysis showed that BCL3 gene alteration frequency was 8%and CNA frequency was 3%,which significantly reduced OS(P=0.0161 and 6.206×10-6,respectively).Finally immunohistochemical confirmed that BCL3 protein was significantly higher expression in the EOC(P<0.001).The expression of nuclear protein was correlated with the local lymph node metastasis(P=0.048),ascites(P=0.035)and differentiation level(P=0.017).Survival analysis found that high or middle expression of BCL3 nuclear protein had a tendency to reduce the survival rate of patients,but the difference did not reach statistical significance(P=0.394).Conclusions:BCL3 mRNA and protein were highly expressed in EOC,and high expression of BCL3 mRNA,BCL3 gene with alteration or CNA reduced OS in patients.BCL3 is a potential therapeutic target in the future.