YAP/TAZ联合应用对预测胆管癌根治性切除术后患者预后的价值分析  

The combination of YAP/TAZ predicts the clinical prognosis in patients with cholangiocarcinoma after radical resection

作　　者：刘颖 吴颖 欧阳育树 何晶晶[2] 沈露俊[2] 齐翰 曹飞 陈双刚 Liu Ying;Wu Ying;Ouyang Yushu;He Jingjing;Shen Lujun;Qi han;Cao Fei;Chen Shuanggang(Department of Radiation Oncology,International Tumor Medical Center,Jinshazhou Hospital of Guangzhou University of Chinese Medicine,Guangzhou 510060,China;department of Minimally Invasive Interventional Therapy,State Key Laboratory of Oncology in South China,Collaborative Innovation Center for Cancer Medicine,Guangzhou 510060,China;department of Intervention,Guangdong Provincial Hospital of Chinese Medicine,the Second Clinical Medical College of Guangzhou University of Chinese Medicine,Guangzhou 510005,China)

机构地区：[1]广州中医药大学金沙洲医院国际肿瘤医疗中心放疗科,510060 [2]中山大学肿瘤防治中心微创介入科,华南肿瘤学国家重点实验室肿瘤医学协同创新中心,广州510060 [3]广州中医药大学第二临床医学院(广东省中医院)介入科,510005

出　　处：《中华内科杂志》2021年第7期637-643,共7页Chinese Journal of Internal Medicine

摘　　要：目的:胆管癌(CCA)是一种来源于胆管上皮细胞的恶性肿瘤,虽然发病率相对较低,但预后极差。YAP(Yes-associated protein)和TAZ(transcription activator with PDZ binding motif)信号传导在维持肿瘤干细胞性中起着关键作用。YAP和TAZ阳性表达在胆管癌中预示着更大的肿瘤和更差的临床预后。本研究评价YAP/TAZ联合应用对预测胆管癌根治性切除术后患者预后的价值分析。方法:回顾性分析2011年1月至2016年6月广州中医药大学金沙洲医院国际肿瘤医疗中心接受过根治性切除术的胆管癌患者的临床信息。并通过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联合应用对总生存期(OS)和无病生存期(DFS)的预测价值。结果:本研究共纳入91例行根治性切除术的胆管癌患者,男性35例、女性56例,年龄60(38~80)岁,中位随访时间为11.0个月,复发率为69.2%,病死率为45.1%,中位OS和DFS分别为10.7个月和8.8个月。YAP/TAZ联合阳性患者比阴性的患者TNM分期更晚(P=0.015)、分化较差(P=0.007)且CA199更高(P=0.031)。多因素Cox分析显示,YAP/TAZ组合阳性是预测根治性切除术后胆管癌患者OS(P=0.010)和DFS(P=0.028)较差的独立预后因素之一。进一步亚组分析标明,YAP/TAZ联合也能有效地预测淋巴结阳性和(或)手术切缘阳性且需要辅助化疗的胆管癌患者的OS(P=0.044)和DFS(P=0.043)。结论:YAP/TAZ联合能有效预测根治性切除后术胆管癌患者的OS和DFS,包括术后需要辅助化疗的高危患者。Objective Cholangiocarcinoma(CCA)is a malignant tumor derived from bile duct epithelial cells with extremely poor prognosis.The Hippo-Yes-associated protein(YAP)/transcription activator with PDZ binding motif(TAZ)signaling plays a critical role in cancer stem cell biology.Previous studies have shown that the positive expression of YAP/TAZ in CCA predicts larger tumor size and unfavorable clinical outcomes.We aim to evaluate the prognostic value of YAP/TAZ detection in CCA patients.Methods CCA patients who underwent radical resection were retrospectively analyzed at our institution from January 2011 to June 2016.Postoperative pathological specimens were scored by YAP/TAZ immunohistochemical staining.The prognostic value of YAP/TAZ was analyzed by multivariate Cox-proportional hazards model.Results A total of 91 CCA patients were enrolled.During a median follow-up time of 11.0 months,69.2%patients relapsed and 45.1%died.The median OS and DFS were 10.7 months and 8.8 months respectively.The YAP/TAZ dual positive patients owned a worse TNM stage(P=0.015),poorer tissue differentiation(P=0.007),and a higher CA199 than those in negative patients.Multivariate Cox analysis identified that YAP/TAZ dual positivity as a significant factor predicted poorer OS(P=0.010)and DFS(P=0.028)in CCA patients after radical resection.In subgroup analysis,YAP/TAZ combination also significantly predicted OS(P=0.044)and DFS(P=0.043)in CCA patients with positive lymphatic metastasis and/or surgical margin who required adjuvant therapy.Conclusions YAP/TAZ positivity is an independent predictive factor for survival in CCA patients after radical resectiony.

关 键 词：胆管上皮癌 预后 YAP/TAZ 

分 类 号：R735.8[医药卫生—肿瘤]