癌基因YAP和TAZ与胰腺恶性肿瘤生物学行为及其预后的关系

Relationship of oncogene YAPand TAZwith biological behavior and prognosis of pancreatic malignant tumors

目的探索胰腺导管腺癌(PDAC)组织中YAP/TAZ表达与临床病理指标的关系,分析YAP/TAZ与根治术后患者预后的关系。方法分析178例公开数据癌症基因组图谱(TCGA)队列PDAC患者有关YAP/TAZ转录组学数据,并回顾性分析2015-12-25-2018-07-02于山东省立医院行胰腺肿瘤切除术的86例PDAC患者临床信息,通过YAP/TAZ免疫组化染色对术后病理标本进行评分。采用Kaplan-Meier方法和Cox比例风险模型分析YAP/TAZ与根治术后患者预后的关系。结果86例患者中26例(30.23%)患者YAP强阳性,40例(46.51%)患者TAZ强阳性。YAP强阳性患者与YAP弱阳性患者1年生存率分别为30.8%和48.3%,2年生存率分别为11.5%和20.0%,P=0.021,YAP强阳性与较差的生存率有关(P=0.021),且YAP阳性综合评分为影响PDAC患者预后生存的危险因素(P=0.029,HR=1.707,95%CI:1.056~2.759);YAP强阳性表达与患者远处转移(P=0.020)和神经侵犯(P=0.036)有关联。结论YAP是PDAC中有价值的预后生物标志物,与根治术后PDAC患者的生存期有关,且YAP表达水平与PDAC患者是否发生远处转移和神经侵犯有关联。

Objective To explore the correlation between the expression of YAP/TAZin pancreatic ductal adenocarcinoma(PDAC)tissue and clinicopathological indicators,and analyze the relationship between YAP/TAZand the prognosis of PDAC patients after radical resection.Methods Publicly available YAP/TAZtranscriptomics data were retrieved from 178PDAC patients from The Cancer Genome Atlas(TCGA).The clinical information of 86PDAC patients who underwent pancreatic tumor resection in Shandong Provincial Hospital from December 25,2015to July 2,2018were retrospectively analyzed,and the postoperative pathological specimens were scored by YAP/TAZimmunohistochemical staining.The prognostic correlation of YAP/TAZwas analyzed by the Kaplan-Meier method and multivariate Coxproportional hazards model.Results HAmong 86patients,26patients(30.23%)were strongly positive for YAP,and 40patients(46.51%)were strongly positive for TAZ.The 1-year survival rates of patients with strong YAP positivity and those with weak YAP positivity were 30.8%and 48.3%respectively,and the 2-year survival rates were 11.5%and 20.0%respectively,P=0.021.Strong YAP positivity was related to poor survival rate(P=0.021),and YAP positive comprehensive score was a risk factor affecting the prognosis and survival of PDAC patients(P=0.029,HR=1.707,95%CI:1.056~2.759);strong YAP positive expression was associated with patients with distant metastasis(P=0.020),nerve invasion(P=0.036).Conclusions YAPis a valuable prognostic biomarker in PDAC,which is related to the survival of PDAC patients after radical surgery,and the expression level of YAP is associated with the occurence of distant metastasis and nerve invasion in PDAC patients.