H4K16乳酸化位点修饰蛋白在乳腺癌中的表达及预后价值  

Expression and prognostic value of h4k16 lactylation site protein in breast cancer

作　　者：燕莎 付毓平 李文涛 朱亚 YAN Sha;FU Yu-ping;LI Wen-tao;ZHU Ya(Department of Laboratory Medicine,Henan Province Hospital of TCM,the Second Affiliated Hospital of Henan University of Chinese Medicine,Zhengzhou 450000,China;School of Medicine laboratory,Sanquan College of Xinxiang Medical University,Xinxiang,Henan 453003,China;Department of Clinical Laboratory,Henan Provincial People's Hospital,Zhengzhou University People's Hospital,Zhengzhou 450003,China)

机构地区：[1]河南省中医院,河南中医药大学第二附属医院检验中心,郑州1450000 [2]新乡医学院三全学院医学检验学院,河南新乡453003 [3]河南省人民医院,郑州大学人民医院检验科,郑州450003

出　　处：《医药论坛杂志》2024年第23期2465-2469,共5页Journal of Medical Forum

基　　金：河南省科技发展计划(222102310645)。

摘　　要：目的探讨组蛋白H4位点16赖氨酸乳酸化修饰(histone H4 site 16 lysine lactylation,H4K16lac)在乳腺癌(breast cancer,BC)中的表达及临床预后价值。方法采用2005年1月至2016年1月的132例乳腺癌患者的高通量癌组织芯片(HBreD132Su07),建立临床资料,包括:患者年龄、性别、肿瘤大小、病理类型、病理分级、临床分期、复发时间以及人类表皮生长因子受体2(human epidermal growth factor receptor 2,HER 2)、P53等表达情况,随访时间3.3~11年,使用HBreD032Su01癌旁芯片共检测癌旁组织32例。基于高通量乳腺癌组织和癌旁组织芯片,通过免疫组化(immunohistochemistry,IHC)检测H4K16lac的表达水平,采用免疫印迹检测H4K16lac在乳腺癌细胞系中的表达,通过Kaplan-Meier法分析H4K16lac高、低表达患者间的生存差异。结果H4K16lac位点修饰蛋白主要表达于乳腺癌癌细胞和癌旁组织细胞的细胞核中。H4K16lac在乳腺癌组织和癌旁组织中的表达阳性率分别为91.67%(121/132)和68.75%(22/32),差异具有统计学意义(P<0.05);基于IHC评分的相对定量分析显示,H4K16lac在乳腺癌组织中表达水平升高,明显高于对应癌旁组织,差异有统计学意义(P<0.001)。MCF-7、MDA-MB-231、MDA-MB-468、HCC1937细胞系中H4K16lac修饰位点蛋白表达水平均高于正常的乳腺细胞系,差异有统计学意义(P<0.001)。相关性分析显示,H4K16lac表达与临床分期,是否复发以及复发生存期相关。生存分析提示低表达H4K16lac的乳腺癌患者较高表达患者更能在5年预后总生存期中获益(P<0.001)。结论H4K16lac修饰蛋白在乳腺癌组织中表达升高,H4K16lac可作为乳腺癌预后评估的重要分子指标。Objective To investigate the expression of histone H4 site 16 lysine lactylation(H4K16lac)in breast cancer(BC)and its clinical prognostic value.Methods A total of 132 BC patients from January 2005 to January 2016 were selected to establish clinical data including age,gender,tumor size,pathological type,pathological grade,clinical stage,recurrence time and expression of HER 2 and P53,etc.The follow-up period was 3.3 to 11 years.HBreD032Su01 paracancer chip contained paracancer tissue in 32 cases.The expression of H4K16lac was detected by immunohistochemistry(IHC)and Western blotting based on high-throughput BC tissue and adjacent tissue microarray as well as BC cell lines.The survival of BC patients(H4K16lac high expression vs.low expression)was analyzed by Kaplan-Meier method.Results The expression of H4K16lac was localized in the nucleus of BC tissue and adjacent tissues.The positive rates of H4K16lac expression in BC and adjacent tissues were 91.67%(121/132),and 68.75%(22/32),respectively,with statistical differences between the two groups(P<0.05);Relative quantitative analysis based on IHC score showed that the relative expression of H4K16lac in BC tissues was higher than that in adjacent tissues(P<0.001).The expression levels of H4K16lac in MCF-7,MDA-MB-231,MDA-MB-468,HCC1937 BC cell lines were higher than that in normal mammary gland cell line(all with P<0.001).Correlation analysis showed that H4K16lac expression was positively correlated with clinical stage,recurrence and recurrence survival span.Survival analysis showed that the prognostic survival time of BC patients with low H4K16lac expressions are more likely to benefit from a 5-year overall survival prognosis than the patients had high H4K16lac expression(P<0.001).Conclusion The expression of H4K16lac is up-regulated in BC tissues,and H4K16lac may be used as an important molecular marker for prognostic evaluation of BC.

关 键 词：乳腺癌 乳酸化 组蛋白 预后 

分 类 号：R737.9[医药卫生—肿瘤]