TEAD4在皮肤基底细胞癌中的表达及意义  

Expression and significance of TEAD4 in skin basal cell carcinoma

作　　者：汪炜[1] 常雅欣 任蓝栋 王宁[2] 白瑞敏 WANG Wei;CHANG Yaxin;REN Landong;WANG Ning;BAI Ruimin(Department of Dermatology,the Second Affiliated Hospital of Xi'an Jiaotong University,Xi'an 710004,China;Department of Dermatology,the First Affiliated Hospital of Xi'an Jiaotong University,Xi'an 710061,China)

机构地区：[1]西安交通大学第二附属医院皮肤科,陕西西安710004 [2]西安交通大学第一附属医院皮肤科,陕西西安710061

出　　处：《大连医科大学学报》2024年第4期295-301,307,共8页Journal of Dalian Medical University

摘　　要：目的探讨转录增强关联域转录因子4(TEAD4)在皮肤基底细胞癌(BCC)和正常皮肤组织中的表达差异,并分析其表达水平与临床特征的相关性以及参与BCC发病的潜在机制。方法收集正常皮肤组织蜡块样本18例和BCC患者蜡块样本60例,通过免疫组化方法检测TEAD4的表达。评估不同临床特征的BCC患者TEAD4的表达差异,纳入的临床特征包括性别、初始诊断BCC的年龄、病程、是否为日光暴露部位、是否为头面部、单发或多发、病理亚型、Clark分级、肿瘤厚度等。使用siRNA特异性地敲低角质形成细胞HaCaT的TEAD4水平,使用实时荧光定量PCR(RT-qPCR)检测TEAD4 mRNA的水平,明确其敲低情况;使用CCK8及7-AAD、PE AnnexinⅤ双染法分别检测其增殖及凋亡情况。结果在正常皮肤组织中,TEAD4阳性表达率为100%,而BCC中,TEAD4阳性表达率只有51.7%,两者比较差异有统计学意义(P<0.001)。在病程<1年的BCC患者中,TEAD4的表达多为阴性,而在病程≥1年的患者中,TEAD4的表达则多为弱阳性;对于病理亚型为微结节型、浅表型、色素型的BCC,TEAD4的表达多为弱阳性或强阳性,而在结节型和浸润型BCC中,TEAD4的表达则多为阴性,差异均有统计学意义(P<0.05)。TEAD4 siRNA转染后,HaCaT细胞中TEAD4的mRNA水平降低了37.83%,差异有统计学意义(P<0.01)。TEAD4敲减组与对照组相比,细胞活力在48 h和72 h分别增加了8.02%和9.10%,凋亡下调了48.63%,差异具有统计学意义(P<0.05)。结论TEAD4在BCC中低表达,发挥抑癌作用,且其表达水平与BCC的临床特征有关。角质形成细胞TEAD4低表达可改变细胞增殖、凋亡等,可能与BCC的发病机制有关。Objective To investigate the expression patterns of transcription enhanced association domain(TEAD4)in both skin basal cell carcinoma(BCC)and normal skin tissues,exploring its correlation with clinical characteristics and potential role in BCC pathogenesis.Methods A total of 18 paraffin-embedded samples of normal skin tissues and 60 paraffin-embedded BCC samples were collected.Immunohistochemistry was employed to assess TEAD4 expression.The association between TEAD4expression levels and various clinical features of BCC patients-including gender,age at initial diagnosis,disease duration,sun exposure sites,head and face involvement,single or multiple lesions,pathological types,Clark grade,and tumor thickness-was analyzed.TEAD4 knockdown in HaCaT cells was achieved using siRNA transfection,followed by RT-qPCR to confirm mRNA suppression.Cell proliferation and apoptosis were evaluated using CCK8 assay and 7-AAD,PE AnnexinⅤdouble staining,respectively.Results TEAD4 expression was detected in 100%of normal skin tissues but only in 51.7%of BCC tissues;the difference was statistically significant(P<0.001).BCC patients with a disease duration of<1 year predominantly showed negative TEAD4 expression,whereas those with≥1 year had mainly weakly positive expression.Among BCC subtypes,micronodular,superficial,and pigmented types mostly exhibited weakly or strongly positive TEAD4 expression,whereas nodular and infiltrative types were predominantly negative.These differences were statistically significant(P<0.05).In HaCaT cells,TEAD4 mRNA levels decreased by 37.83%following TEAD4 siRNA transfection(P<0.01).Cell viability in the TEAD4knockdown group increased by 8.02%at 48 hours and 9.10%at 72 hours,while apoptosis was reduced by 48.63%,compared to controls(P<0.05).These findings demonstrate significant biological effects of TEAD4 knockdown.Conclusion TEAD4 expression is notably reduced in BCC tissues,suggesting a potential tumor suppressive role.Moreover,TEAD4 expression correlates with various clinical features of BCC.The d

关 键 词：皮肤基底细胞癌 TEAD4 角质形成细胞 增殖 凋亡 

分 类 号：R758.6[医药卫生—皮肤病学与性病学]