TNFAIP6在口腔疣状癌与口腔鳞状细胞癌中的表达及其与临床病理的关系

Expression of TNFAIP6 in oral verrucous carcinoma and oral squamous cell carcinoma and its relationship with clinicopathology

目的:研究口腔疣状癌(OVC)及口腔鳞状细胞癌(OSCC)中肿瘤坏死因子α诱导蛋白6(TNFAIP6)的表达其与临床病理的关系。方法:在TCGA数据库中下载OSCC的RNA-seq数据,采用两样本t检验比较TNFAIP6在OSCC和正常口腔黏膜中的表达差异,采用受试者工作曲线(ROC)和生存曲线分别评价其诊断和预后价值。取15例正常口腔黏膜、22例OVC和24例OSCC及对应癌旁组织,利用免疫组织化学方法检测上述标本中TNFAIP6的表达和分布,并分析其阳性表达率与临床病理因素的关系。取5例OSCC、3例OVC及对应癌旁组织,利用反转录聚合酶链反应、免疫印迹技术验证其转录及蛋白表达水平,使用Graph Pad Prism 7.0软件进行计量数据分析,采用SPSS 21.0软件包对各组间数据进行两样本均数t检验。结果:在TCGA数据库中,TNFAIP6在OSCC中表达显著上调且具有一定的诊断价值,然而其表达失调与OSCC患者总体生存率无关。在OSCC石蜡标本中,TNFAIP6表达显著上调,与饮酒、颈淋巴结转移、临床分期有关。在OVC石蜡标本中,TNFAIP6表达显著上调;TNFAIP6在OSCC癌组织的转录及蛋白表达显著上调。结论:TNFAIP6在OSCC组织中异常高表达,并与诊断及预后相关,可作为肿瘤分子标志物。

PURPOSE:To investigate the expression of tumor necrosis factorα–induced protein 6(TNFAIP6)in oral verrucous carcinoma(OVC)and oral squamous cell carcinoma(OSCC),and its relationship with clinicopathology.METHODS:RNA-seq data of OSCC was downloaded from the TCGA database.Paired t test was used to compare the expression of TNFAIP6 from OSCC and normal oral mucosa.Receiver operating characteristic curve(ROC)and KaplanMeier curve were drawn to evaluate its diagnostic and prognostic value,respectively.Fifteen cases of normal oral mucosa(NM),22 cases of OVC and 24 cases of OSCC paraffin specimens were used for TNFAIP6 detection by immunohistochemistry;furthermore,the relationships between the positive expression rate and clinical factors was analyzed.Five pairs of OSCC cancer and adjacent tissues,5 pairs of OVC cancer and adjacent tissues were verified by reverse transcription polymerase chain reaction and Western blotting.The measurement data was analyzed using Graph Pad Prism 7.0 software,and paired t test was used for comparison between groups with SPSS 21.0 software package.RESULTS:In the TCGA database,the expression of TNFAIP6 was significantly up-regulated in OSCC and had certain diagnostic value.The expression of TNFAIP6 in OSCC paraffin specimens was significantly up-regulated,which was related to alcohol consumption,cervical lymph node metastasis and clinical stage.The expression of TNFAIP6 in OVC paraffin specimens was significantly up-regulated,which was related to the size of the primary tumor.TNFAIP6 was significantly up-regulated in transcription and protein expression in OSCC tumor tissues.All the above results were statistically significant(P<0.05).CONCLUSIONS:TNFAIP6 is highly expressed in OSCC tissues and associated with diagnosis and prognosis,which can be used as a molecular marker for OSCC.