Annals of Surgical Oncology

, Volume 21, Supplement 4, pp 721–728

High STAT4 Expression is a Better Prognostic Indicator in Patients with Hepatocellular Carcinoma After Hepatectomy

  • Gizachew Yismaw Wubetu
  • Tohru Utsunomiya
  • Daichi Ishikawa
  • Shinichiro Yamada
  • Tetsuya Ikemoto
  • Yuji Morine
  • Shuichi Iwahashi
  • Yu Saito
  • Yusuke Arakawa
  • Satoru Imura
  • Mami Kanamoto
  • Chengzhan Zhu
  • Yoshimi Bando
  • Mitsuo Shimada
Translational Research and Biomarkers



Signal transducer and activator of transcription 4 (STAT4) mediates the intracellular effects of interleukin-12, leading to the production of interferon gamma (IFN-γ) and natural killer cells cytotoxicity. However, the clinical significance of STAT4 expression in patients with hepatocellular carcinoma (HCC) remains virtually unknown.


A total of 66 HCC patients who underwent hepatectomy were enrolled in this study. Quantitative real-time polymerase chain reaction was performed to determine STAT4 and IFNG mRNA expression levels. Tissue microarray-based immunohistochemistry was performed to examine CD8+ T cells, STAT4, and INF-γ proteins.


STAT4 was differentially expressed in tumor and nontumor tissues (P = 0.001) and positively correlated with IFNG expression (R2 = 0.506, P < 0.05) and CD8+ T cell infiltration (R2 = 0.53, P < 0.001). Significant correlations were observed between STAT4 expression and tumor TNM stage (P = 0.043), hepatic venous invasion (P = 0.003), des-gamma-carboxy prothrombin (P = 0.011), tumor size (P = 0.036), and tumor differentiation (P = 0.034). Patients with high STAT4 expression had significantly better recurrence-free survival (P = 0.009). Low STAT4 expression (P = 0.030) and presence of portal venous invasion or hepatic venous invasion (P = 0.006) were independent risk factors for HCC recurrence.


Downregulation of STAT4 in HCC indicated aggressive tumor behavior and predicted a worse clinical outcome. STAT4 might be a useful biomarker to identify patients at high risk of recurrence after hepatectomy.

Supplementary material

10434_2014_3861_MOESM1_ESM.docx (14 kb)
Supplementary material 1 (DOCX 13 kb)
10434_2014_3861_MOESM2_ESM.docx (15 kb)
Supplementary material 2 (DOCX 14 kb)


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Copyright information

© Society of Surgical Oncology 2014

Authors and Affiliations

  • Gizachew Yismaw Wubetu
    • 1
  • Tohru Utsunomiya
    • 1
  • Daichi Ishikawa
    • 1
  • Shinichiro Yamada
    • 1
  • Tetsuya Ikemoto
    • 1
  • Yuji Morine
    • 1
  • Shuichi Iwahashi
    • 1
  • Yu Saito
    • 1
  • Yusuke Arakawa
    • 1
  • Satoru Imura
    • 1
  • Mami Kanamoto
    • 1
  • Chengzhan Zhu
    • 1
  • Yoshimi Bando
    • 2
  • Mitsuo Shimada
    • 1
  1. 1.Department of SurgeryThe University of TokushimaTokushimaJapan
  2. 2.Department of PathologyThe University of TokushimaTokushimaJapan

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