口腔鳞状细胞癌中ETV4的表达模式及其临床意义  

Expression pattern of ETV4 and its clinicopathological significance in oral squamous cell carcinoma

作　　者：虞颖娟 张伟[2] YU Yingjuan;ZHANG Wei(Department of Oral Implantology,Changzhou Stomotological Hospital,Changzhou 213003,China;Department of Oral and Maxillofacial Surgery,The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University,Huai'an 223300,China)

机构地区：[1]常州市口腔医院种植科,江苏常州213003 [2]南京医科大学附属淮安第一人民医院口腔颌面外科,江苏淮安223300

出　　处：《口腔生物医学》2024年第6期328-334,共7页Oral Biomedicine

基　　金：南京医科大学科技发展基金(NMUB20220213,NMUB20-220206)。

摘　　要：目的:探索ETS转录因子4(ETV4)在口腔鳞状细胞癌(OSCC)中的表达及临床意义。方法:采用生物信息学分析检测ETV4在OSCC及正常组织中的表达水平,揭示ETV4表达与患者预后之间的关系;构建靶向ETV4的小干扰RNA,在Cal27细胞中敲低ETV4,通过Western blot实验验证敲低效率;利用克隆形成实验检测敲低ETV4对Cal27细胞增殖的影响;通过细胞迁移实验、细胞侵袭实验及流式细胞术分别检测敲低ETV4对Cal27细胞迁移、侵袭及凋亡的影响;利用Western blot实验检测敲低ETV4后上皮间充质转化(EMT)相关标志物蛋白水平的变化;通过基因集合富集分析(GSEA)分析探索癌症基因组图谱头颈鳞癌数据库(TCGA-HNSCC)中ETV4高低表达两组患者差异基因富集的通路。结果:生物信息学分析结果显示ETV4在OSCC中高表达(P<0.05);ETV4表达水平与患者总体生存率显著相关(P<0.05);靶向敲低ETV4可抑制Cal27细胞增殖、侵袭和迁移能力,促进Cal27细胞的凋亡(P<0.05);敲低ETV4可抑制Cal27细胞的EMT过程;TCGA中ETV4高低表达患者的差异基因主要富集在EMT,参与HNSCC的发展。结论:ETV4在OSCC中高表达,可作为OSCC患者生存预后的生物学标志物。ETV4促进OSCC细胞增殖、迁移、侵袭和EMT过程,抑制OSCC细胞凋亡。Objective:To explore the expression and clinicopathologic significance of E26 transformation-specific variant transcription factor 4(ETV4)in oral squamous cell carcinoma(OSCC).Methods:The expression level of ETV4 in OSCC and normal oral mucosa epithelial tissues were determined by bioinformatics analysis,which revealed the relationship between the expression of ETV4 and the prognosis of OSCC patients.We constructed a small interfering RNA targeting ETV4 to knockdown ETV4 in Cal27 cells.Western blot experiments were utilized to verify the knockdown efficiency.The effect of ETV4 silencing on the proliferation of Cal27 cells was tested by clone formation assay.The effects of ETV4 silencing on cell migration,invasion and apoptosis of Cal27 cells were examined by migration assay,invasion assay and flow cytometry analysis.Western blot experiment was utilized to examine changes in protein levels of epithelial-mesenchymal transition(EMT)related marker after ETV4 knockdown.GSEA analysis was used to explore the pathway of differential gene enrichment between two groups of patients with high and low expression of ETV4 in TCGA-HNSCC.Results:Bioinformatics analysis showed that ETV4 was highly expressed in OSCC tissues(P<0.05);The expression level of ETV4 was significantly correlated with overall survival rate of patients(P<0.05);Targeted silencing of ETV4 inhibited the proliferation,invasion and migration of Cal27 cells and promoted the apoptosis of Cal27 cells(P<0.05);Targeted silencing of ETV4 inhibited the EMT process in Cal27 cells.The differentially expressed genes were mainly enriched in the pathways of EMT and HNSCC between two groups of patients.Conclusions:ETV4 is highly expressed in OSCC and can be utilized as a biomarker for survival prognosis in OSCC patients.ETV4 positively regulates the proliferation,migration,invasion and EMT of OSCC cells,and is negatively correlated with the apoptosis of OSCC cells.

关 键 词：口腔鳞状细胞癌 E-26转化特异性变异转录因子4 细胞表型 上皮间充质转化 

分 类 号：R780.2[医药卫生—口腔医学]