目的 :检测Yes相关蛋白(Yes-associated protein,YAP)在口腔鳞状细胞癌(oral squamous cell carcinoma,OSCC)中的表达及临床意义,判断其是否与肿瘤细胞的侵袭和迁移特性相关。方法:利用免疫组织化学染色检测68例原发口腔鳞癌患者组织标本中YAP的表达情况,分析其与各临床病理因素之间的关系;构建靶向YAP的sh RNA以及存在特定位点突变的YAP过表达载体,转染含YAP蛋白的TB2T4和SCC23口腔鳞癌细胞;利用细胞划痕实验和细胞侵袭实验检测YAP干扰及过表达对肿瘤细胞迁移和侵袭能力的影响。采用SPSS18.0软件包对数据进行统计学处理。结果:在原发口腔鳞癌组织中,YAP在细胞核和胞质的表达均显著高于正常口腔黏膜上皮组织(P〈0.05)。YAP在细胞核的表达情况与患者颈淋巴结转移(P〈0.001)及5年总体生存率(P=0.008)显著相关。沉默YAP基因后,TB2T4和SCC23细胞的迁移和侵袭能力受到显著抑制(P〈0.05);过表达YAP基因后,肿瘤细胞的迁移和侵袭能力得到部分恢复(P〈0.05)。结论:YAP的表达与口腔鳞癌患者颈淋巴结转移及预后相关,YAP在口腔鳞癌细胞的侵袭、迁移中可能发挥重要作用。
PURPOSE: To investigate the expression of YAP(Yes-associated protein) in oral squamous cell carcinoma(OSCC) and determine if YAP was associated with tumor cell invasion and migration. METHODS: Sixty-eight primary OSCC patients were enrolled in this study. YAP expression in tissue specimens was investigated by immunohistochemistry staining. YAP putback plasmid with specific mutation sites after YAP-sh RNA interference was constructed by site-directed mutagenesis. Cell scratch and cell invasion assay were performed after YAP-si RNA interference or YAP putback again in TB2T4 and SCC23 cells. The data was analyzed using SPSS18.0 software package. RESULTS: Nuclear and cytoplasmic expression of YAP was increased in primary OSCC tissue samples(P〈0.05). Nuclear expression of YAP was associated with cervical lymph node metastasis(P〈0.001) and 5-year overall survival rate(P=0.008). YAP knockdown greatly suppressed tumor cell migration and cell invasion both in TB2T4 and SCC23 cells(Scramble vs YAP-sh RNA, P〈0.01), but these abilities were rescued subtotally when YAP was put back to the YAP-sh RNA stable cells(Control vs YAP putback, P〈0.01). CONCLUSION: YAP expression in OSCC was associated with cervical lymph node metastasis and YAP might play an essential role on the invasion ability of OSCC cells.