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High leukocyte mtDNA content contributes to poor prognosis through ROS-mediated immunosuppression in hepatocellular carcinoma patients

Compelling epidemiological evidences indicate a significant association between leukocyte mitochondrial DNA (mtDNA) content and incidence risk of several malignancies, including hepatocellular carcinoma (HCC). However, whether leukocyte mtDNA content affect prognosis of HCC patients and underlying m...

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Autores principales: He, Xianli, Qu, Falin, Zhou, Feng, Zhou, Xingchun, Chen, Yibing, Guo, Xu, Li, Jibin, Huang, Qichao, Yang, Yefa, Lyu, Zhuomin, Zhang, Hongxin, Xing, Jinliang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5008404/
https://www.ncbi.nlm.nih.gov/pubmed/26985767
http://dx.doi.org/10.18632/oncotarget.8071
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author He, Xianli
Qu, Falin
Zhou, Feng
Zhou, Xingchun
Chen, Yibing
Guo, Xu
Li, Jibin
Huang, Qichao
Yang, Yefa
Lyu, Zhuomin
Zhang, Hongxin
Xing, Jinliang
author_facet He, Xianli
Qu, Falin
Zhou, Feng
Zhou, Xingchun
Chen, Yibing
Guo, Xu
Li, Jibin
Huang, Qichao
Yang, Yefa
Lyu, Zhuomin
Zhang, Hongxin
Xing, Jinliang
author_sort He, Xianli
collection PubMed
description Compelling epidemiological evidences indicate a significant association between leukocyte mitochondrial DNA (mtDNA) content and incidence risk of several malignancies, including hepatocellular carcinoma (HCC). However, whether leukocyte mtDNA content affect prognosis of HCC patients and underlying mechanism has never been explored. In our study, leukocyte mtDNA content was measured in 618 HCC patients and its prognostic value was analyzed. Moreover, we detected the immunophenotypes of peripheral blood mononuclear cells (PBMCs) and plasma concentrations of several cytokines in 40 HCC patients and assessed the modulating effects of mtDNA content on immunosuppression in cell models. Our results showed that HCC patients with high leukocyte mtDNA content exhibited a significantly worse recurrence-free survival (RFS) and overall survival (OS) than those with low leukocyte mtDNA content. Leukocyte mtDNA content and TNM stage exhibited a notable joint effect in prognosis prediction. Furthermore, we found that patients with high leukocyte mtDNA content exhibited a higher frequency of CD4(+)CD25(+)FOXP3(+) regulatory T (Treg) cells and lower frequency of NK cells in PBMCs and had higher TGF-β1 and lower TNF-α and IFN-γ plasma concentration when compared with those with low leukocyte mtDNA content, which suggests an immunosuppressive status. High leukocyte mtDNA content significantly enhanced the ROS-mediated secretion of TGF-β1, which accounted for higher Treg and lower NK frequency in PBMCs. In a conclusion, our study for the first time demonstrates that leukocyte mtDNA content is an independent prognostic marker complementing TNM stage and associated with an ROS-mediated immunosuppressive phenotype in HCC patients.
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spelling pubmed-50084042016-09-12 High leukocyte mtDNA content contributes to poor prognosis through ROS-mediated immunosuppression in hepatocellular carcinoma patients He, Xianli Qu, Falin Zhou, Feng Zhou, Xingchun Chen, Yibing Guo, Xu Li, Jibin Huang, Qichao Yang, Yefa Lyu, Zhuomin Zhang, Hongxin Xing, Jinliang Oncotarget Research Paper Compelling epidemiological evidences indicate a significant association between leukocyte mitochondrial DNA (mtDNA) content and incidence risk of several malignancies, including hepatocellular carcinoma (HCC). However, whether leukocyte mtDNA content affect prognosis of HCC patients and underlying mechanism has never been explored. In our study, leukocyte mtDNA content was measured in 618 HCC patients and its prognostic value was analyzed. Moreover, we detected the immunophenotypes of peripheral blood mononuclear cells (PBMCs) and plasma concentrations of several cytokines in 40 HCC patients and assessed the modulating effects of mtDNA content on immunosuppression in cell models. Our results showed that HCC patients with high leukocyte mtDNA content exhibited a significantly worse recurrence-free survival (RFS) and overall survival (OS) than those with low leukocyte mtDNA content. Leukocyte mtDNA content and TNM stage exhibited a notable joint effect in prognosis prediction. Furthermore, we found that patients with high leukocyte mtDNA content exhibited a higher frequency of CD4(+)CD25(+)FOXP3(+) regulatory T (Treg) cells and lower frequency of NK cells in PBMCs and had higher TGF-β1 and lower TNF-α and IFN-γ plasma concentration when compared with those with low leukocyte mtDNA content, which suggests an immunosuppressive status. High leukocyte mtDNA content significantly enhanced the ROS-mediated secretion of TGF-β1, which accounted for higher Treg and lower NK frequency in PBMCs. In a conclusion, our study for the first time demonstrates that leukocyte mtDNA content is an independent prognostic marker complementing TNM stage and associated with an ROS-mediated immunosuppressive phenotype in HCC patients. Impact Journals LLC 2016-03-14 /pmc/articles/PMC5008404/ /pubmed/26985767 http://dx.doi.org/10.18632/oncotarget.8071 Text en Copyright: © 2016 He et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
He, Xianli
Qu, Falin
Zhou, Feng
Zhou, Xingchun
Chen, Yibing
Guo, Xu
Li, Jibin
Huang, Qichao
Yang, Yefa
Lyu, Zhuomin
Zhang, Hongxin
Xing, Jinliang
High leukocyte mtDNA content contributes to poor prognosis through ROS-mediated immunosuppression in hepatocellular carcinoma patients
title High leukocyte mtDNA content contributes to poor prognosis through ROS-mediated immunosuppression in hepatocellular carcinoma patients
title_full High leukocyte mtDNA content contributes to poor prognosis through ROS-mediated immunosuppression in hepatocellular carcinoma patients
title_fullStr High leukocyte mtDNA content contributes to poor prognosis through ROS-mediated immunosuppression in hepatocellular carcinoma patients
title_full_unstemmed High leukocyte mtDNA content contributes to poor prognosis through ROS-mediated immunosuppression in hepatocellular carcinoma patients
title_short High leukocyte mtDNA content contributes to poor prognosis through ROS-mediated immunosuppression in hepatocellular carcinoma patients
title_sort high leukocyte mtdna content contributes to poor prognosis through ros-mediated immunosuppression in hepatocellular carcinoma patients
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5008404/
https://www.ncbi.nlm.nih.gov/pubmed/26985767
http://dx.doi.org/10.18632/oncotarget.8071
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