首页|H4K16乳酸化位点修饰蛋白在乳腺癌中的表达及预后价值

H4K16乳酸化位点修饰蛋白在乳腺癌中的表达及预后价值

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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。
Expression and prognostic value of h4k16 lactylation site protein in breast cancer
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 be-tween 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 clin-ical stage,recurrence and recurrence survival span.Survival analysis showed that the prognostic survival time of BC pa-tients with low H4K16lac expressions are more likely to benefit from a 5-year overall survival prognosis than the pa-tients 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.

Breast cancerLactylationHistone proteinPrognosis

燕莎、付毓平、李文涛、朱亚

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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 450000

新乡医学院三全学院医学检验学院,河南新乡 453003

河南省人民医院,郑州大学人民医院检验科,郑州 450003

乳腺癌 乳酸化 组蛋白 预后

2024

医药论坛杂志
中华预防医学会,河南省医学情报研究所

医药论坛杂志

影响因子:0.47
ISSN:1672-3422
年,卷(期):2024.45(23)