Cell-free circulating mitochondrial DNA content and risk of hepatocellular carcinoma in patients with chronic HBV infection.

Authors

Ling Li, Division of Population Science, Department of Medical Oncology, Thomas Jefferson UniversityFollow
Hie-Won Hann, Thomas Jefferson University, Jefferson Medical CollegeFollow
Shaogui Wan, Thomas Jefferson UniversityFollow
Richard Hann, Liver Disease Prevention CenterFollow
Chun Wang, Division of Population Science, Department of Medical Oncology, Thomas Jefferson University; Department of Environmental Health, School of Public Health, Nantong UniversityFollow
Yinzhi Lai, Division of Population Science, Department of Medical Oncology, Kimmel Cancer Center, Thomas Jefferson UniversityFollow
Xishan Ye, Division of Population Science, Department of Medical Oncology, Thomas Jefferson University
Alison Evans, Division of Population Science, Department of Medical Oncology, Thomas Jefferson University
Ronald E. Myers, PhD, DSW, Director, Division of Population Science, and Professor, Department of Medical Oncology, Jefferson Medical CollegeFollow
Zhong Ye, Division of Population Science, Department of Medical Oncology, Kimmel Cancer Center, Thomas Jefferson UniversityFollow
Bingshan Li, Center for Human Genetics Research, Department of Molecular Physiology and Biophysics, Vanderbilt UniversityFollow
Jinliang Xing, Experimental Teaching Center, School of Basic Medicine, Fourth Military Medical UniversityFollow
Hushan Yang, Division of Population Science, Department of Medical Oncology, Thomas Jefferson UniversityFollow

Document Type

Article

Publication Date

4-11-2016

Comments

This article has been peer reviewed. It was published in: Scientific Reports.

Volume 6, 11 April 2016, Article number 23992.

The published version is available at DOI: 10.1038/srep23992

Copyright © 2016, Macmillan Publishers Limited

This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

Abstract

Recent studies have demonstrated a potential link between circulating cell-free mitochondrial DNA (mtDNA) content and cancers. However, there is no study evaluating the association between circulating mtDNA as a non-invasive marker of hepatocellular carcinoma (HCC) risk. We conducted a nested case-control study to determine circulating mtDNA content in serum samples from 116 HBV-related HCC cases and 232 frequency-matched cancer-free HBV controls, and evaluate the retrospective association between mtDNA content and HCC risk using logistic regression and their temporal relationship using a mixed effects model. HCC cases had significantly lower circulating mtDNA content than controls (1.06 versus 2.47, P = 1.7 × 10(-5)). Compared to HBV patients with higher mtDNA content, those with lower mtDNA content had a significantly increased risk of HCC with an odds ratio (OR) of 2.19 (95% confidence interval [CI] 1.28-3.72, P = 0.004). Quartile analyses revealed a significant dose-dependent effect (Ptrend = 0.001) for this association. In a pilot longitudinal sub-cohort of 14 matched cases-control pairs, we observed a trend of dramatically decreased mtDNA content in cases and slightly decreased mtDNA content in controls, with a significant interaction of case-control status with time (Pinteraction = 0.049). Our findings suggest that circulating mtDNA is a potential novel non-invasive biomarker of HCC risk in HBV patients.

Recommended Citation

Li, Ling; Hann, Hie-Won; Wan, Shaogui; Hann, Richard; Wang, Chun; Lai, Yinzhi; Ye, Xishan; Evans, Alison; Myers, PhD, DSW, Ronald E.; Ye, Zhong; Li, Bingshan; Xing, Jinliang; and Yang, Hushan, "Cell-free circulating mitochondrial DNA content and risk of hepatocellular carcinoma in patients with chronic HBV infection." (2016). Department of Medicine Faculty Papers. Paper 160.
https://jdc.jefferson.edu/medfp/160

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 License.

PubMed ID

27063412