摘要
目的探讨三阴性乳腺癌(TNBC)组织中组蛋白去乙酰化酶3(HDAC3)的表达及临床预后价值。方法从癌症基因组图谱(TCGA)数据库下载三阴性乳腺癌转录组和临床数据,使用R和Perl软件进行数据分析整理,采用非参数的Mann-Whitney U检验分析基因HDAC3的差异表达,Kaplan-Meier和Cox回归分析三阴性乳腺癌患者预后影响因素。基因集富集分析(GSEA)方法分析基因HDAC3的调控网络,探究潜在机制。结果基因HDAC3在合并淋巴结转移的三阴性乳腺癌组织中的表达量高于非合并淋巴结转移的三阴性乳腺癌组织(Z=-2.273,P<0.05),高表达HDAC3的TNBC生存时间缩短的风险是低表达HDAC3的TNBC的1.440倍[风险比(HR)=1.440,95%可信区间(CI):1.033~2.007,P<0.01],高表达HDAC3的TNBC无进展生存时间缩短的风险是低表达HDAC3的TNBC的1.424倍(HR=1.424,95%CI:1.014~2.000,P<0.01);HDAC3表达量与NFKB(R=0.334,P<0.01)和Snail(R=0.148,P<0.05)的表达量正相关;GSEA分析提示HDAC3参与上皮-间充质转化(EMT)(NES=1.407,P<0.01)和NFKB(NES=1.481,P<0.05)信号通路的激活。结论HDAC3在三阴性乳腺癌组织中高表达,与患者的不良预后密切相关,其可能通过NFKB-Snail信号通路在三阴性乳腺癌中发挥促癌作用。
Objective To investigate the expression and clinical prognostic value of histone deacetylase 3(HDAC3)in triple-negative breast cancer(TNBC)tissues.Methods Transcriptional and clinical data of TNBC were downloaded from The Cancer Genome Atlas(TCGA)database.R and Perl software were used for data analysis and processing.The non-parametric Mann-Whitney U test was performed to analyze the differential expression of the HDAC3 gene.Kaplan-Meier and Cox regression analyses were conducted to identify prognostic factors in triple-negative breast cancer patients.Gene set enrichment analysis(GSEA)was performed to explore the potential mechanisms of HDAC3.The statistical analysis was performed using R software,with a significance level set at P<0.05 to indicate statistically significant differences.Results The expression level of gene HDAC3 was higher in TNBC tissues with combined lymph node metastasis than those without combined lymph node metastasis(Z=-2.273,P<0.05).The risk of shorter survival time in TNBC with high HDAC3 expression was 1.440 times higher than TNBC with low HDAC3 expression[hazard ratio(HR)=1.440,95%confidence interval(CI):1.033-2.007,P<0.01].Similarly,the risk of shorter progression-free survival time in TNBC with high HDAC3 expression was 1.424 times higher than that in TNBC with low HDAC3 expression(HR=1.424,95%CI:1.014-2.000,P<0.01).The expression level of HDAC3 was positively correlated with the expression levels of NFKB(R=0.334,P<0.01)and Snail(R=0.148,P<0.05).GSEA analysis indicated the involvement of HDAC3 in the activation of the epithelial-mesenchymal transition(EMT)pathway(NES=1.407,P<0.01)and the NFKB signaling pathway(NES=1.481,P<0.05).Conclusion HDAC3 is highly expressed in TNBC tissues and closely associated with poor prognosis.It may play a pro-carcinogenic role in TNBC through the NFKB-Snail signaling pathway.
作者
吴坤琳
林伟
严乾壹
王德星
缪秀英
张惠灏
Wu Kunlin;Lin Wei;Yan Qianyi;Wang Dexing;Miao Xiuying;Zhang Huihao(Department of Thyroid and Breast Surgery,the First Affiliated Hospital,Fujian Medical University,Fuzhou 350005,China;Department of General Surgery,Second Division,National Regional Medical Center,Binhai Campus of the First Affiliated Hospital,Fujian Medical University,Fuzhou 350212,China;First Clinical Medical College,Fujian Medical University,Fuzhou 350005,China)
出处
《中华实验外科杂志》
CAS
北大核心
2023年第9期1820-1822,共3页
Chinese Journal of Experimental Surgery
基金
福建省自然科学基金项目(2022J01698)
福建省卫健委中青年骨干人才培养项目。
