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

Wang,Xu; Xin,Wenbin; Zhang,Hua; Zhang,Fengmei; Gao,Meilan; Yuan,Lingling; Xu,Xiaoyan; Hu,Xuemei; Zhao,Mingdong

doi:10.3892/mmr.2014.2510

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

Authors:
- Xu Wang
- Wenbin Xin
- Hua Zhang
- Fengmei Zhang
- Meilan Gao
- Lingling Yuan
- Xiaoyan Xu
- Xuemei Hu
- Mingdong Zhao
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Affiliations: Department of Radiology, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, Shandong 264003, P.R. China, Department of Interventional Radiology, Heze Municipal Hospital, Heze, Shandong 274031, P.R. China, School Hospital, Binzhou Medical University, Yantai, Shandong 264003, P.R. China, Department of Clinical Laboratory, Binzhou Affiliated Hospital of Binzhou Medical University, Binzhou, Shandong 256603, P.R. China, Department of Immunology, Binzhou Medical University, Yantai, Shandong 264003, P.R. China
Published online on: August 21, 2014 https://doi.org/10.3892/mmr.2014.2510
Pages: 2649-2656

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Abstract

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+ and CD8+ T cells relates to HCC pathogenesis remains unclear. In this study, the expression of p-STAT3 in CD4+ and CD8+ 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+ and CD8+ 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+ and CD8+ 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+ and CD8+ T cells of HCC patients, and which may result in abnormal immune surveillance and thereby, contribute to HCC pathogenesis.

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