High STAT4 expression is a better prognostic indicator in patients with hepatocellular carcinoma after hepatectomy.

Abstract

BACKGROUND:

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.

METHODS:

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.

RESULTS:

STAT4 was differentially expressed in tumor and nontumor tissues (P = 0.001) and positively correlated with IFNG expression (R (2) = 0.506, P < 0.05) and CD8(+) T cell infiltration (R (2) = 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.

CONCLUSIONS:

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.

• Authors: 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
• Journal: Annals of surgical oncology (Ann Surg Oncol) Vol. 21 Suppl 4 Pg. S721-8 (Dec 2014) ISSN: 1534-4681 [Electronic] United States
• PMID: 24965572 (Publication Type: Journal Article)

Chemical References

• Biomarkers
• IFNG protein, human
• Protein Precursors
• RNA, Messenger
• STAT4 Transcription Factor
• STAT4 protein, human
• acarboxyprothrombin
• Interferon-gamma
• Prothrombin

Topics

• Adult
• Aged
• Aged, 80 and over
• Biomarkers (blood)
• Blood Vessels (pathology)
• CD8-Positive T-Lymphocytes
• Carcinoma, Hepatocellular (chemistry, genetics, pathology, surgery)
• Disease-Free Survival
• Female
• Follow-Up Studies
• Gene Expression
• Hepatectomy
• Humans
• Interferon-gamma (analysis, genetics)
• Liver (chemistry)
• Liver Neoplasms (chemistry, genetics, pathology, surgery)
• Lymphocyte Count
• Male
• Middle Aged
• Neoplasm Grading
• Neoplasm Invasiveness
• Neoplasm Recurrence, Local (pathology)
• Neoplasm Staging
• Prospective Studies
• Protein Precursors (blood)
• Prothrombin
• RNA, Messenger (analysis)
• STAT4 Transcription Factor (analysis, genetics)
• Tumor Burden