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The signature of liver cancer in immune cells DNA methylation

2018; BioMed Central; Volume: 10; Issue: 1 Linguagem: Inglês

10.1186/s13148-017-0436-1

1868-7083

Yonghong Zhang, Sophie Petropoulos, Jinhua Liu, David Cheishvili, Rudy Zhou, Sergiy Dymov, Kang Li, Ning Li, Moshe Szyf,

Cancer Immunotherapy and Biomarkers

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