Yang Xin-Wei, Li Liang, Hou Guo-Jun, Yan Xin-Zhou, Xu Qin-Guo, Chen Lei, Zhang Bao-Hua, Shen Feng
Department of Laparoscopy, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China.
International Co-operation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute, Second Military Medical University, Shanghai 200438, China.
Oncotarget. 2017 Jan 31;8(5):7710-7721. doi: 10.18632/oncotarget.13846.
Signal transducer and activator of transcription 3 (STAT3) promotes tumor progression in many types of cancer. In this study, we analyzed the prognostic value of this marker in human intrahepatic cholangiocarcinoma (ICC). Using real-time PCR, western blot and immunohistochemistry assays, we found that STAT3 is overexpressed in ICC patients. STAT3 expression correlated with several clinicopathological features, including tumor size, pathological satellite, vascular invasion, undifferentiated-type histology, lymph node metastasis and TNM stage in two independent cohorts of ICC patients. Patients with high STAT3 levels had a poor prognosis in terms of overall survival (OS) and disease-free survival (DFS). Multivariate survival analysis indicated that STAT3 is an independent prognostic factor for OS and DFS. Furthermore, we observed that STAT3 overexpression promotes the invasion, metastasis and proliferation of ICC cells in vitro and in vivo, and also promotes STAT3 phosphorylation. These findings suggest that STAT3 expression correlated negatively with surgical outcome and inhibition of STAT3 expression may constitute a novel target for the treatment of ICC patients.
信号转导与转录激活因子3（STAT3）在多种癌症中促进肿瘤进展。在本研究中，我们分析了该标志物在人肝内胆管癌（ICC）中的预后价值。通过实时PCR、蛋白质免疫印迹和免疫组织化学分析，我们发现STAT3在ICC患者中过表达。在两个独立的ICC患者队列中，STAT3表达与多种临床病理特征相关，包括肿瘤大小、病理卫星灶、血管侵犯、未分化型组织学、淋巴结转移和TNM分期。STAT3水平高的患者在总生存期（OS）和无病生存期（DFS）方面预后较差。多变量生存分析表明，STAT3是OS和DFS的独立预后因素。此外，我们观察到STAT3过表达在体外和体内促进ICC细胞的侵袭、转移和增殖，并且还促进STAT3磷酸化。这些发现表明，STAT3表达与手术结果呈负相关，抑制STAT3表达可能构成治疗ICC患者的新靶点。
