局部晚期口腔鳞状细胞癌YAP1表达及临床意义

The expression and clinical significance of YAP1 in locally advanced oral squamous cell carcinoma

目的探讨Yes相关蛋白1(YAP1)判断局部晚期口腔鳞状细胞癌(LAOSCC)新辅助同步放化疗(CCRT)疗效的意义。方法收集2016年2月至2018年6月间我院手术切除后行新辅助CCRT治疗的109例LAOSCC患者及83例健康志愿者(对照组)。免疫组织化学(IHC)染色法检测YAP1蛋白表达,实时荧光定量PCR(qPCR)检测唾液YAP1 mRNA相对表达量。评价疗效,分为CR、PR、SD、PD。CR+PR定义为治疗缓解,SD+PD定义为治疗无缓解。随访患者总生存期(OS)。结果109例LAOSCC患者获CR 21例、PR 52例,PD 13例、SD 23例。缓解组患者YAP1蛋白评分显著低于无缓解组患者[108.53分(89.82,128.21)vs.134.65分(103.71,144.57),P<0.05]。ROC曲线分析,YAP1蛋白评分预测新辅助CCRT疗效的AUC为0.806(95%CI:0.711~0.900),最佳截断值为131.21分。YAP1蛋白表达与TNM分期和存活情况有关(P<0.05),与其他均无关。与对照组比较,LAOSCC组患者基线唾液YAP1 mRNA相对表达量普遍更高[1.04(0.72,1.14)vs.1.30(1.01,1.70),P<0.001]。Logistic回归分析显示仅YAP1蛋白评分是影响新辅助CCRT疗效的独立因素(P<0.05)。与基线值比较,缓解组唾液YAP1 mRNA相对表达量降低,无缓解组升高。基线唾液YAP1 mRNA相对表达量与YAP1蛋白IHC评分呈正相关(r s=0.245,P=0.010)。YAP1蛋白低表达组患者的中位OS为58个月(14~60个月),高表达组为24个月(8.5~63个月),差异有统计学意义(P=0.018)。结论组织YAP1蛋白IHC高评分与LAOSCC患者新辅助CCRT治疗无缓解及低OS有关,唾液YAP1 mRNA相对表达也与LAOSCC发生及新辅助CCRT治疗反应相关。

Objective To investigate the significance of Yes associated protein 1(YAP1)in evaluating the efficacy of neoadjuvant synchronous radiotherapy and chemotherapy(CCRT)in locally advanced oral squamous cell carcinoma(LAOSCC).Methods One hundred and nine LAOSCC patients and 83 healthy volunteers(control group)who underwent neoadjuvant CCRT treatment after surgical resection in our hospital from February 2016 to June 2018 were collected.Immunohistochemical(IHC)staining was used to detect the expression of YAP1 protein,and real-time quantitative PCR(qPCR)was used to detect the relative expression of YAP1 mRNA in saliva.Evaluate the efficacy and divide it into CR,PR,SD,and PD.CR+PR is defined as treatment response,SD+PD is defined as treatment without response.Follow up the total survival time(OS)of patients.Results Among 109 LAOSCC patients,21 were CR,52 were PR,13 were PD,and 23 were SD.The YAP1 protein score of patients in the remission group was significantly lower than that of patients in the non remission group[108.53(89.82,128.21)vs.134.65(103.71,144.57),P<0.05].ROC curve analysis showed that the AUC of YAP1 protein score for predicting the efficacy of neoadjuvant CCRT was 0.806(95%CI:0.711-0.900),with an optimal cutoff value of 131.21 points.The expression of YAP1 protein is related to staging and survival(P<0.05),but not to any other factors.Compared with the control group,the relative expression of YAP1 mRNA in baseline saliva of patients in the LAOSCC group was generally higher[1.04(0.72,1.14)vs.1.30(1.01,1.70),P<0.001].Logistic regression analysis showed that only YAP1 protein score was an independent factor affecting the efficacy of neoadjuvant CCRT(P<0.05).Compared with baseline values,the relative expression of YAP1 mRNA in saliva decreased in the remission group,while it increased in the non remission group.The relative expression of YAP1 mRNA in baseline saliva was positively correlated with the IHC score of YAP1 protein(r s=0.245,P=0.010).The median OS of patients with low expression of YAP1 protein was 58 months(14-60 months),while those with high expression were 24 months(8.5-63 months),with a statistically significant difference(P=0.018).Conclusion The high score of tissue YAP1 protein IHC is associated with no response and low OS in LAOSCC patients treated with neoadjuvant CCRT.The relative expression of saliva YAP1 mRNA is also associated with the occurrence of LAOSCC and the response to neoadjuvant CCRT treatment.