HDAC5在口腔鳞状细胞癌中的表达及意义  

Expression and significance of HDAC5 in oral squamous cell carcinoma

作　　者：何奋军 林芬 陈雪英[2] HE Fenjun;LIN Fen;CHEN Xueying(Department of Oral and Maxillofacial Surgery,Zhongshan Stomatological Hospital,Zhongshan City,Zhongshan 528400,China;Department of Stomatology,Sixth Affiliated Hospital of Sun Yatsen University,Guangzhou 510000,China)

机构地区：[1]中山市口腔医院口腔颌面外科,广东中山528400 [2]中山大学附属第六医院口腔科,广东广州510000

出　　处：《口腔疾病防治》2024年第12期925-932,共8页Journal of Prevention and Treatment for Stomatological Diseases

基　　金：广东省自然科学基金项目(2019A1515011334)。

摘　　要：目的探讨组蛋白去乙酰化酶5(histone deacetylase 5,HDAC5)在口腔鳞状细胞癌(oral squamous cell carcinoma,OSCC)中的表达情况及临床意义,为OSCC靶向治疗提供研究基础。方法在癌症基因组图谱(the cancer genome atlas,TCGA)数据库中筛选OSCC患者的样本资料,采用受试者工作特征(receiver operating characteristic,ROC)曲线分析来评估HDAC5在OSCC中的预后价值。同时使用Kaplan⁃Meier分析HDAC5与OSCC患者预后的相关性。通过基因本体论(gene oncology,GO)、京都基因及基因组百科全书(kyoto encyclopedia of genes and genomes,KEGG)探究HDAC5在OSCC中发挥的潜在作用。获得单位伦理委员会批准,收集49例OSCC患者癌组织及癌旁组织的石蜡标本及临床信息,应用免疫组织化学(immunohistochemical,IHC)检测HDAC5在OSCC中的表达水平,同时分析HDAC5与OSCC患者临床病理特征之间的关系。结果HDAC5的表达可以用来评估OSCC患者的预后(AUC=0.743)。HDAC5高表达与OSCC患者总生存率低显著相关(P<0.05),同时病理学分级G3/G4中HDAC5表达高的OSCC患者(P=0.022)、T3/T4期中HDAC5表达高的OSCC患者(P=0.028)及有淋巴结转移的HDAC5表达高的OSCC患者(P=0.019)具有更低的生存率。GO及KEGG富集分析显示与HDAC5差异表达的基因主要富集在轴突生成、神经胞体的形成、胶原纤维的合成、神经活性配体⁃受体相互作用、门控通道活动及细胞外基质⁃受体相互作用途径上(P<0.05)。IHC结果显示HDAC5在OSCC中高表达(P<0.05),HDAC5高表达组具有更高的T分期(P=0.041)及淋巴结转移率(P=0.010)。结论HDAC5在OSCC中高表达,并能评估OSCC的预后,具有作为OSCC治疗靶点的潜力。Objective To explore the expression and clinical significance of histone deacetylase 5(HDAC5)in oral squamous cell carcinoma(OSCC)and provide a research basis for targeted therapy of HDAC5.Methods Screening sample data of OSCC patients in TCGA database,and receiver operating characteristic(ROC)curve analysis was used to evaluate the prognostic value of HDAC5 in OSCC.Kaplan⁃Meier analysis was also used to analyze the correlation be⁃tween HDAC5 and the prognosis of OSCC patients.Further,Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)analyses were used to explore the potential role of HDAC5 in OSCC.Finally,the study was ap⁃proved by the ethics committee and the expression level of HDAC5 in OSCC was detected by immunohistochemistry(IHC),while the relationship between HDAC5 and the clinical pathological characteristics of OSCC patients was analyzed.Results The expression of HDAC5 can be used to assess the prognosis of OSCC patients(AUC=0.743).High ex⁃pression of HDAC5 was significantly correlated with low survival probability in OSCC patients(P<0.05).OSCC pa⁃tients with high HDAC5 expression in G3/G4 pathological grading(P=0.022),OSCC patients with high HDAC5 expres⁃sion in the T3/T4 stage(P=0.028),and OSCC patients with high HDAC5 expression in lymph node metastasis(P=0.019)had lower survival probability.GO and KEGG enrichment analyses showed that genes differentially expressed with HDAC5 were mainly enriched in axon generation,neuronal cell body formation,collagen fiber synthesis,neuroactive li⁃gand receptor interactions,gated channel activity,and extracellular matrix(ECM)⁃receptor interaction pathways(P<0.05).The IHC results showed that HDAC5 was highly expressed in OSCC(P<0.05).The high expression group of HDAC5 had higher T staging(P=0.041)and lymph node metastasis(P=0.010).Conclusion HDAC5 is highly ex⁃pressed in OSCC and can predict the prognosis of OSCC,and HDAC5 could serve as a therapeutic target for OSCC.

关 键 词：口腔鳞状细胞癌 组蛋白去乙酰化转移酶 组蛋白去乙酰化转移酶5 基因富集分析 肿瘤预后 肿瘤分子标记物 生物信息学分析 免疫组织化学 

分 类 号：R78[医药卫生—口腔医学]