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

Research paper by Gizachew Yismaw GY Wubetu, Tohru T Utsunomiya, Daichi D Ishikawa, Shinichiro S Yamada, Tetsuya T Ikemoto, Yuji Y Morine, Shuichi S Iwahashi, Yu Y Saito, Yusuke Y Arakawa, Satoru S Imura, Mami M Kanamoto, Chengzhan C Zhu, Yoshimi Y Bando, Mitsuo M Shimada

Indexed on: 27 Jun '14Published on: 27 Jun '14Published in: Annals of Surgical Oncology



Abstract

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 (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.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.