赖氨酸单甲基转移酶SETD8上调三阴性乳腺癌细胞程序性死亡因子配体1蛋白表达及其临床意义

Upregulation of programmed death ligand 1 protein expression by SET domain-containing protein 8 indicates poor prognosis in triple negative breast cancer

目的探讨赖氨酸单甲基转移酶SETD8对三阴性乳腺癌(TNBC)细胞程序性死亡因子配体1(PD-L1)表达的影响及其对临床预后的意义。方法构建SETD8基因沉默及过表达TNBC细胞株MDA-MB-231,实时定量聚合酶链反应(Real-time PCR)和蛋白质印迹法(Western blot)检测TNBC稳转细胞PD-L1基因及蛋白表达改变并采用t检验比较PD-L1基因及蛋白表达改变的差异。免疫组织化学检测112例TNBC组织内SETD8与PD-L1表达,Spearman等级相关分析SETD8与PD-L1表达的相关性,Kaplan-Meier生存分析法分析癌组织内SETD8表达高低对三阴性乳腺癌预后的影响。结果SETD8上调TNBC细胞PD-L1蛋白表达,而PD-L1mRNA表达改变不明显;112例TNBC乳腺癌患者中PD-L1和SETD8有45例共同高表达,29例为共同低表达,SETD8与PD-L1表达呈正相关(r=0.301,P<0.05),SETD8高表达提示TNBC的5年总生存率为58.7%,显著低于SETD8低表达的77.8%(χ^2=4.509,P<0.05)。结论SETD8上调TNBCPD-L1表达,SETD8高表达提示TNBC的5年总生存率显著降低。

Objective To explore the role of SET domain-containing protein 8 (SETD8) in upregulation of programmed death ligand 1 (PD-L1) and its significance in prognosis of triple negative breast cancer (TNBC). Methods Detecting the different expression of PD-L1 mRNA and protein in MDA-MB-231 with SETD8 knockdown or overexpression by real-time quantitative polymerase chain reaction (Real-time PCR) and Western blotting. Detecting the co-expression of SETD8 and PD-L1 in 112 cases of TNBC patients by immunohistochemistry and analyzing their correlation. Statistically analyzing the survival significance of SETD8 expression in TNBC patients. Results PD-L1 protein, other than PD-L1 mRNA is significantly increased by SETD8 in MDA-MB-231 cells;In 112 TNBC cases, SETD8 is highly coexpressed is positively correlated with PD-L1 in TNBC (r=0.301, P<0.05). The 5-year overall survival in SETD8 high expression group is 58.7%, which is significantly lower than it (77.8%)in SETD8 low expression group (χ^2=4.509, P<0.05). Conclusion PD-L1 protein expression is upregulated by SETD8 in MDA-MB-231 breast cancer cells. High SETD8 expression in TNBC is an indicator for poor prognosis.