Aberrant expression of p-STAT3 in peripheral blood [CD4.sup.+] and [CD8.sup.+] T cells related to hepatocellular carcinoma development

• Published in: Molecular medicine reports Vol. 10; no. 5; p. 2649
• Main Authors: Wang, Xu, Xin, Wenbin, Zhang, Hua, Zhang, Fengmei, Gao, Meilan, Yuan, Lingling, Xu, Xiaoyan, Hu, Xuemei, Zhao, Mingdong
• Format: Journal Article
• Language: English
• Published: Spandidos Publications 01.11.2014
• Subjects: Cancer; Development and progression; Gene expression; Genetic aspects; Genetic research; Hepatoma; Oncology, Experimental; Properties; Transcription factors
• ISSN: 1791-2997; 1791-3004
• DOI: 10.3892/mmr.2014.2510

Hepatocellular carcinoma (HCC) is one of the most common cancer types worldwide. The signal transducer and activator of transcription 3 (STAT3) protein is a member of the STAT transcription factor family. Oncogenesis, invasion, and metastasis of HCC are associated with activation of STAT3. However, whether aberrant expression of phosphorylated STAT3 (p-STAT3) in peripheral [CD4.sup.+] and [CD8.sup.+] T cells relates to HCC pathogenesis remains unclear. In this study, the expression of p-STAT3 in [CD4.sup.+] and [CD8.sup.+] T cells, and the levels of interferon-γ (IFN-γ), interleukin-4 (IL-4), IL-6 and IL-10 in the human hepatoma cell line Huh7 co-cultured with peripheral blood mononucleated cells (PBMCs) of healthy volunteers were measured. The correlations between p-STAT3 and IFN-γ/IL-4, IFN-γ, IL-4, IL-6 and IL-10 were then analyzed. Results showed that the p-STAT3 level is higher in [CD4.sup.+] and [CD8.sup.+] T cells in the peripheral blood of HCC patients, and in PBMCs co-cultured with Huh7 cells compared to controls. The cytokine (IL-4, IL-6 and IL-10) levels were increased and the IFN-γ level was decreased in the serum of HCC patients and in supernatants of PBMCs co-cultured with Huh7 cells. Correlation analyses demonstrated that the IFN-γ/IL-4 ratio and the IFN-γ level negatively correlate to the p-STAT3 level in [CD4.sup.+] and [CD8.sup.+] T cells in samples from patients and in cells cultured in vitro. By contrast, the levels of IL-4, IL-6 and IL-10 positively correlated to the p-STAT3 level. This study indicated that the expression of p-STAT3 is upregulated in peripheral [CD4.sup.+] and [CD8.sup.+] T cells of HCC patients, and which may result in abnormal immune surveillance and thereby, contribute to HCC pathogenesis. Key words: p-STAT3, peripheral blood, [CD4.sup.+] T cells, [CD8.sup.+] T cells, immune surveillance, pathogenesis, hepatocellular carcinoma