High leukocyte mtDNA content contributes to poor prognosis through ROS-mediated immunosuppression in hepatocellular carcinoma patients
Immunosuppression
DOI:
10.18632/oncotarget.8071
Publication Date:
2016-03-14T18:55:37Z
AUTHORS (12)
ABSTRACT
// Xianli He 1, * , Falin Qu 2, Feng Zhou 1 Xingchun 2 Yibing Chen Xu Guo Jibin Li Qichao Huang Yefa Yang 3 Zhuomin Lyu 4 Hongxin Zhang Jinliang Xing Department of General Surgery, Tangdu Hospital, The Fourth Military Medical University, Xi'an 710032, China State Key Laboratory Cancer Biology and Experimental Teaching Center Basic Medicine, Radioactive Intervention, Eastern Hepatobiliary Surgery Second Shanghai 200438, Pain Treatment, These authors have contributed equally to this work Correspondence to: Xing, e-mail: xingjl@fmmu.edu.cn Keywords: mitochondrial DNA content, hepatocellular carcinoma, prognosis, reactive oxygen species, immunosuppression Received: November 10, 2015 Accepted: February 23, 2016 Published: March 14, ABSTRACT Compelling epidemiological evidences indicate a significant association between leukocyte (mtDNA) content incidence risk several malignancies, including carcinoma (HCC). However, whether mtDNA affect prognosis HCC patients underlying mechanism has never been explored. In our study, was measured in 618 its prognostic value analyzed. Moreover, we detected the immunophenotypes peripheral blood mononuclear cells (PBMCs) plasma concentrations cytokines 40 assessed modulating effects on cell models. Our results showed that with high exhibited significantly worse recurrence-free survival (RFS) overall (OS) than those low content. Leukocyte TNM stage notable joint effect prediction. Furthermore, found higher frequency CD4 + CD25 FOXP3 regulatory T (Treg) lower NK PBMCs had TGF-β1 TNF-α IFN-γ concentration when compared which suggests an immunosuppressive status. High enhanced ROS-mediated secretion TGF-β1, accounted for Treg PBMCs. conclusion, study first time demonstrates is independent marker complementing associated phenotype patients.
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