STAT3 overexpression promotes metastasis in intrahepatic cholangiocarcinoma and correlates negatively with surgical outcome

Yang Xin-wei; Li Liang; Hou Guo-jun; Yan Xin-zhou; Xu Qin-guo; Chen Lei; Zhang Bao-hua; Shen Feng

doi:10.18632/oncotarget.13846

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Research Papers:

STAT3 overexpression promotes metastasis in intrahepatic cholangiocarcinoma and correlates negatively with surgical outcome

Yang Xin-wei, Li Liang, Hou Guo-jun, Yan Xin-zhou, Xu Qin-guo, Chen Lei, Zhang Bao-hua _ and Shen Feng

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Oncotarget. 2017; 8:7710-7721. https://doi.org/10.18632/oncotarget.13846

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Abstract

Yang Xin-wei1,*, Li Liang2,*, Hou Guo-jun3,*, Yan Xin-zhou1, Xu Qin-guo3, Chen Lei2, Zhang Bao-hua1, Shen Feng4

1Department of Laparoscopy, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China

2International Co-operation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute, Second Military Medical University, Shanghai 200438, China

3Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China

4Department of Comprehensive Treatment, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China

*These authors contributed equally to this work

Correspondence to:

Zhang Bao-hua, email: [email protected]

Keywords: intrahepatic cholangiocarcinoma, STAT3, prognosis, proliferation, metastasis

Received: May 23, 2016 Accepted: November 30, 2016 Published: December 09, 2016

ABSTRACT

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.

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Research Papers:

STAT3 overexpression promotes metastasis in intrahepatic cholangiocarcinoma and correlates negatively with surgical outcome

Abstract