A novel prediction model for human papillomavirus-associated oropharyngeal squamous cell carcinoma using p16 and subcellular β-catenin expression.
A novel prediction model for human papillomavirus-associated oropharyngeal squamous cell carcinoma using p16 and subcellular β-catenin expression.
复制标题
使用 p16 和亚细胞 β-连环蛋白表达的人乳头瘤病毒相关口咽鳞状细胞癌的新预测模型。
DOI：
10.1111/jop.12378
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发表时间：
2016
期刊：
影响因子：
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通讯作者：
Chen,ZhuoGeorgia
中科院分区：
文献类型：
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作者：
Qian,Guoqing;Hu,Zhongliang;Xu,Hong;Müller,Susan;Wang,Dongsheng;Zhang,Hongzheng;Kim,Sungjin;Chen,Zhengjia;Saba,NabilF;Shin,DongM;Wang,AndrewY;Chen,ZhuoGeorgia
p16过表达是一种高度敏感但特异性中等的生物标志物，可用于预测人乳头瘤病毒（HPV）相关的口咽鳞状细胞癌（OPSCC）。核β-连环蛋白易位与HPV阳性OPSCC有关。然而，β-catenin与p16相结合的策略是否可以更好地预测HPV相关的OPSCC.MethodsWe评估的表达p16和β-catenin（核和膜）免疫组化染色在101 OPSCC组织和HPV状态的HPV DNA原位杂交。Logistic回归模型用于评估HPV预测的单个或多个生物标志物。结果单因素分析显示，p16和核β-catenin与HPV感染状态呈正相关，而膜β-catenin与HPV感染状态呈负相关（P<0. 01）。p16显示出最高的HPV预测能力，曲线下面积（AUC）为0.9074，而核β-连环蛋白和膜β-连环蛋白分别为0.6762和0.7635，表明HPV预测的差异准确性。多变量分析显示p16与HPV显著相关，而核和膜β-catenin显示边缘显著性。三生物标志物模型同样敏感（98.9% vs. 100%）但更具体（88.9% vs. 81%）比单独p16，这也显示了良好的预测价值，（P= 0.0002）生存和无病（P= 0.0158）生存率。结论我们的研究提出了一种结合p16和亚细胞β-连环蛋白预测HPV相关OPSCC的新模型，这一发现值得进一步验证。
Backgroundp16 overexpression is a highly sensitive yet moderately specific biomarker for predicting human papillomavirus (HPV)‐associated oropharyngeal squamous cell carcinoma (OPSCC). Nuclear β‐catenin translocation has been linked to HPV‐positive OPSCC. However, whether the strategy of combining β‐catenin with p16 can better predict HPV‐associated OPSCC remains unknown.MethodsWe evaluated the expression of p16 and β‐catenin (nuclear and membrane) by immunohistochemistry staining in 101 OPSCC tissues and HPV status by HPV DNAin situhybridization. Logistic regression models were used to evaluate single or multiple biomarkers for HPV prediction. The prediction power, sensitivity, and specificity were determined by receiver operating characteristic (ROC) analyses.ResultsOur data showed that upon univariate analysis, p16 and nuclear β‐catenin were positively correlated with HPV status, while membrane β‐catenin was inversely correlated with HPV status (P< 0.01). p16 showed the highest HPV predictive power, with area under the curve (AUC) of 0.9074 compared to 0.6762 for nuclear β‐catenin and 0.7635 for membrane β‐catenin, respectively, indicating differential accuracies for HPV prediction. Multivariable analysis showed that p16 was significantly correlated with HPV, while nuclear and membrane β‐catenin showed marginal significance. The three‐biomarker model was similarly sensitive (98.9% vs. 100%) but more specific (88.9% vs. 81%) than p16 alone, which also showed a good predictive value for overall (P= 0.0002) survival and disease‐free (P= 0.0158) survival.ConclusionOur study suggests a novel model of combining p16 and subcellular β‐catenin for prediction of HPV‐associatred OPSCC, and this finding deserves further validation.