YAP1、PD-L1及MMR蛋白在消化道神经内分泌癌中的表达及意义

Expression and Clinical Significance of YAP1 , PD-L1 and MMR Proteins inNeuroendocrine Carcinoma of Digestive Tract

目的探讨Yes相关蛋白1(YAP1)、程序性死亡-配体1(PD-L1)及错配修复(MMR)蛋白在消化道神经内分泌癌组织中的表达及临床意义。方法应用组织芯片及免疫组化法,检测122例消化道神经内分泌癌组织中YAP1、PD-L1及MMR蛋白的表达情况,并结合消化道神经内分泌癌不同临床病理参数和患者预后进行比较分析。结果YAP1核、YAP1质、PD-L1及MMR蛋白缺失的阳性率分别为27.1%、35.3%、22.1%、2.5%。YAP1在神经内分泌癌组织中的表达显著高于正常组织或神经内分泌瘤(均P<0.05),YAP1核表达与脉管浸润、淋巴结转移及TNM分期呈显著正相关(均P<0.05)。PD-L1表达与临床病理特征无明显相关性(均P>0.05)。相关性分析显示YAP1核表达与PD-L1表达呈负相关(P<0.05)。生存分析未发现YAP1及PD-L1的预后意义。结论YAP1核表达可能与消化道神经内分泌癌的发生发展有关;消化道神经内分泌癌表达PD-L1及错配修复缺陷(dMMR);针对YAP1的靶向治疗及抗PD-1/PD-L1治疗可能成为消化道神经内分泌癌的潜在新疗法。

Objective To investigate the expression and clinical significance of Yesassociated protein 1(YAP1),pro-grammed cell death protein ligand 1(PD-L1)and mismatch repair(MMR)proteins in neuroendocrine carcinomas of the digestive tract.Methods The expression of YAP1,PD-L1 and MMR proteins in 122 cases of neuroendocrine carcinomas of the digestive tract was detected by tissue microarray and immunohistochemical method.The findings were compared with clinical and patho-logical parameters and patient outcome.Results The positive expression rates of YAP1 nulcear,YAP1 cytoplasm,PD-L1 and.MMR proteins in neuroendocrine carcinomas of the digestive tract were 27.1%(33/122),35.3%(43/122),22.1%(27/122)and 2.5%(3/122),respectively.The expression rate of YAP1 in neuroendocrine carcinoma was significantly higher than that in nor-mal tissues or neuroendocrine tumors(P<0.05).YAP1 nuclear expression was positively related to vascular invasion,lymph node metastasis and TNM stage(P<0.05).PD-L1 expression was not correlated with clinicopathological features(P>0.05).Spearman correlation analysis showed a negative correlation between YAP1 nuclear and PD-L1 expression(r=-0.199,P=0.035).Survival analysis did not find the prognostic significance of YAP1 and PD-L1.Conclusion YAP1 nulcear expression may play an important role in the pathogenesis of neuroendocrine carcinomas of the digestive tract.Neuroendocrine carcinomas of the digestive tract express PD-L1 and show mismatch repair protein deficiency.Targeting YAP1 and anti-PD-1/PD-L1 thera-py may become potential new methods.