title: Aberrant expression of p-STAT3 in peripheral blood CD4+ and CD8+ T cells related to hepatocellular carcinoma development.
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.
authors.affiliation: Department of Radiology, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, Shandong 264003, P.R. China.
authors.forename: Xu
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Radiology, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, Shandong 264003, P.R. China.
authors.forename: Wenbin
authors.initials: W
authors.lastname: Xin
authors.affiliation: Department of Interventional Radiology, Heze Municipal Hospital, Heze, Shandong 274031, P.R. China.
authors.forename: Hua
authors.initials: H
authors.lastname: Zhang
authors.affiliation: School Hospital, Binzhou Medical University, Yantai, Shandong 264003, P.R. China.
authors.forename: Fengmei
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Department of Clinical Laboratory, Binzhou Affiliated Hospital of Binzhou Medical University, Binzhou, Shandong 256603, P.R. China.
authors.forename: Meilan
authors.initials: M
authors.lastname: Gao
authors.affiliation: Department of Radiology, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, Shandong 264003, P.R. China.
authors.forename: Lingling
authors.initials: L
authors.lastname: Yuan
authors.affiliation: Department of Immunology, Binzhou Medical University, Yantai, Shandong 264003, P.R. China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Xu
authors.affiliation: Department of Immunology, Binzhou Medical University, Yantai, Shandong 264003, P.R. China.
authors.forename: Xuemei
authors.initials: X
authors.lastname: Hu
authors.affiliation: Department of Radiology, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, Shandong 264003, P.R. China.
authors.forename: Mingdong
authors.initials: M
authors.lastname: Zhao
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism*; D063646:Carcinogenesis; D006528:Carcinoma, Hepatocellular / Q000097:blood*; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D006801:Humans; D007371:Interferon-gamma / Q000097:blood; D007378:Interleukins / Q000097:blood; D008113:Liver Neoplasms / Q000097:blood*; D010750:Phosphoproteins / Q000097:blood; D050796:STAT3 Transcription Factor / Q000097:blood*
chemical_list: D007378:Interleukins; D010750:Phosphoproteins; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D007371:Interferon-gamma