乳腺癌中N-α-乙酰转移酶10的表达及预后意义

Expression and prognosis of N-α-acetyltransferase gene 10 in breast cancer

目的探讨蛋白质N-α-乙酰转移酶基因10(NAA10)作为乳腺癌治疗靶点的可能性。方法通过METABRIC数据库分析33个乙酰转移酶基因与乳腺癌预后的关系,并分析NAA10基因表达与乳腺癌临床病理参数之间的关系;反转录-聚合酶链反应(RT-PCR)和蛋白质印迹法(Western blot)实验检测NAA10基因mRNA和蛋白水平表达,应用NAA10小干扰RNA(siRNA)处理NAA10高表达的乳腺癌细胞株,选取乳腺癌国际联盟分子分类(METABRIC)数据库1974例乳腺癌患者,其中腺腔A型(Luminal A)718例,腺腔B型(Luminal B)占488例,人表皮生长因子受体2(Her-2)过表达型占240例,基底样型(Basal-like)占329例,正常乳腺样型(Normal-like)199例。通过细胞计数试剂盒(CCK-8)和平板克隆形成实验检测NAA10基因沉默后对乳腺癌细胞增殖的影响。计数资料比较采用t检验、χ^2检验,相关性检验采用Spearman等级相关分析,。结果NAA10的mRNA表达与乳腺癌的无病生存率(DFS)及总生存率(OS)差异有统计学意义(P<0.05),其相对风险比分别为1.31(1.14~1.51),1.13(1.01~1.25);NAA10基因的表达与乳腺癌组织学分级、淋巴结状态、诺丁汉指数(NPI)明显正相关(P<0.01);NAA10的mRNA和蛋白水平在Basal-like型乳腺癌表达最高;与对照组比较,NAA10基因沉默可以抑制乳腺癌细胞增殖50%左右(P<0.05),差异有统计学意义。结论NAA10基因与乳腺癌细胞增殖密切相关且其表达水平与乳腺癌预后关系密切。

Objective To study the possibility of protein acetyltransferase gene 10(NAA10)as a target for breast cancer treatment.Methods Based on METABRIC database,1974 cases of breast cancer patients were selected,including 718 cases of Luminal A subtype,488 cases of Luminal B subtype,240 cases of human epidermalgrowth factor receptor-2(Her-2)subtype,329 cases of basal-like subtype,and 199 cases of normal-like subtype.Using METABRIC database,the relationship between 33 acetyltransferase genes and the prognosis of breast cancer,and the relationship between NAA10 gene expression and clinicopathological parameters of breast cancer were studied.NAA10 small interfering RNA(siRNA)was used to treat breast cancer cell lines with NAA10 high expression,and the effect of NAA10 gene silencing on breast cancer cell proliferation was detected by cell counting kit-8(CCK-8)and plate clone formation assays.Results The mRNA expression of NAA10 was significantly correlated with the disease-free survival rate(DFS)and overall survival rate of breast cancer(P<0.05),and the relative risk ratios were 1.31(1.14-1.51)and 1.13(1.01-1.25),respectively.NAA10 gene expression was positively correlated with breast cancer histological grade,lymph node status,and Nottingham index(NPI)(P<0.01).NAA10 mRNA and protein levels were highest in Basal-like breast cancer.Compared with control group,NAA10 gene silencing inhibited 50%breast cancer cell proliferation(P<0.05).Conclusion NAA10 gene is closely related to breast cancer cell proliferation and its expression level is closely related to breast cancer prognosis.NAA10 gene may become a target for future treatment of breast cancer.