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Clin Epigenetics. 2018 Jan 18;10:8. doi: 10.1186/s13148-017-0436-1. eCollection 2018.

The signature of liver cancer in immune cells DNA methylation.

Author information

1
1Beijing Youan Hospital, Capital Medical School, Beijing, China.
2
2Department of Pharmacology and Therapeutics, McGill University, 3655 Sir William Osler Promenade, Montreal, Quebec H3G 1Y6 Canada.
3
3Deparment of Clinical Science, Karolinska Institutet, Alfred Nobels Allé 8, 141 52 Huddinge, Sweden.
4
Montreal EpiTerapia Inc., 4567 Cecile, H9K1N2, Montreal, QC Canada.
#
Contributed equally

Abstract

Background:

The idea that changes to the host immune system are critical for cancer progression was proposed a century ago and recently regained experimental support.

Results:

Herein, the hypothesis that hepatocellular carcinoma (HCC) leaves a molecular signature in the host peripheral immune system was tested by profiling DNA methylation in peripheral blood mononuclear cells (PBMC) and T cells from a discovery cohort (n = 69) of healthy controls, chronic hepatitis, and HCC using Illumina 450K platform and was validated in two validation sets (n = 80 and n = 48) using pyrosequencing.

Conclusions:

The study reveals a broad signature of hepatocellular carcinoma in PBMC and T cells DNA methylation which discriminates early HCC stage from chronic hepatitis B and C and healthy controls, intensifies with progression of HCC, and is highly enriched in immune function-related genes such as PD-1, a current cancer immunotherapy target. These data also support the feasibility of using these profiles for early detection of HCC.

KEYWORDS:

DNA methylation; Hepatocellular carcinoma; Immune functions; Peripheral white blood cells

Conflict of interest statement

Informed consent has been obtained from all participants and the study received ethical approval from The Capital Medical School in Beijing and McGill University (IRB Study Number A02-M34-13B).Participants/patients have given their consent for their data to be published in the report.The authors declare that MS, YZ, SP, and NL have applied for patent protection, MS has equity in HKG epitherapeutics and Montreal epiterapia, and DC has equity in Montreal epiterapia.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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