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

Oncotarget. 2017 Jan 31;8(5):7710-7721. doi: 10.18632/oncotarget.13846.

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.

Keywords: STAT3; intrahepatic cholangiocarcinoma; metastasis; prognosis; proliferation.

MeSH terms

  • Adult
  • Aged
  • Bile Duct Neoplasms / genetics
  • Bile Duct Neoplasms / metabolism*
  • Bile Duct Neoplasms / pathology
  • Bile Duct Neoplasms / surgery*
  • Cell Differentiation
  • Cell Line, Tumor
  • Cell Movement*
  • Cell Proliferation
  • Chi-Square Distribution
  • Cholangiocarcinoma / genetics
  • Cholangiocarcinoma / metabolism*
  • Cholangiocarcinoma / secondary
  • Cholangiocarcinoma / surgery*
  • Disease-Free Survival
  • Female
  • Gene Expression Regulation, Neoplastic
  • Hepatectomy* / adverse effects
  • Humans
  • Kaplan-Meier Estimate
  • Lymphatic Metastasis
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Neoplasm Staging
  • Phosphorylation
  • Proportional Hazards Models
  • Risk Factors
  • STAT3 Transcription Factor / genetics
  • STAT3 Transcription Factor / metabolism*
  • Signal Transduction
  • Time Factors
  • Treatment Outcome
  • Tumor Burden
  • Up-Regulation

Substances

  • STAT3 Transcription Factor
  • STAT3 protein, human