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STATs profiling reveals predominantly-activated STAT3 in cholangiocarcinoma genesis and progression

Hasaya Dokduang1, Anchalee Techasen, Nisana Namwat

  • 1Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand; Liver Fluke and Cholangiocarcinoma Research Center, Khon Kaen University, Khon Kaen, Thailand.

Journal of Hepato-Biliary-Pancreatic Sciences
|July 22, 2014
PubMed
Abstract

Insights

Signal transducer and activator of transcription (STAT) 3 is key in liver fluke-induced cholangiocarcinoma (CCA) inflammation and progression. STAT3 activation correlates with poor prognosis in CCA patients, suggesting its potential as a prognostic marker.

Area of Science:

  • Oncology
  • Immunology
  • Parasitology

Background:

  • Investigated aberrant Signal Transducer and Activator of Transcription (STAT) family expression in human and Opisthorchis viverrini (Ov)-induced hamster cholangiocarcinoma (CCA).
  • Examined STAT family members including STAT1, STAT2, STAT3, STAT4, STAT5a, STAT5b, and STAT6.

Purpose of the Study:

  • To elucidate the role of STAT family members in CCA development and progression.
  • To determine the association between STAT expression, inflammation, and patient prognosis.

Main Methods:

  • Immunohistochemistry was used to profile STAT expression and phosphorylation in human and hamster CCA tissues.
  • Investigated STAT5 localization in macrophages and STAT3 activation in CCA cells mediated by lipopolysaccharide (LPS)-induced macrophage-conditioned media.

Main Results:

  • STAT1-4 and STAT6 were found in hyperplastic bile ducts and tumor cells; STAT5a and STAT5b were located in macrophages and connective tissues.
  • STAT3 and STAT5b expression correlated with poorer histological differentiation and shorter patient survival.
  • STATs expression increased during carcinogenesis in hamsters, particularly with marked inflammation at 30 days post-infection, linking inflammation to STAT activation.

Conclusions:

  • STAT3 is the primary STAT involved in inflammation contributing to CCA carcinogenesis and progression.
  • STAT3 activation is predominantly observed in CCA cell lines.
  • STAT3 may serve as a valuable prognostic marker for poor outcomes in CCA patients.
Keywords:
CholangiocarcinomaInflammationSignal transducer and activator of transcription 3

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