1Beijing Youan Hospital, Capital Medical School, Beijing, China.
2Department of Pharmacology and Therapeutics, McGill University, 3655 Sir William Osler Promenade, Montreal, Quebec H3G 1Y6 Canada.
Clin Epigenetics. 2018 Jan 18;10:8. doi: 10.1186/s13148-017-0436-1. eCollection 2018.
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 ( = 69) of healthy controls, chronic hepatitis, and HCC using Illumina 450K platform and was validated in two validation sets ( = 80 and = 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 , a current cancer immunotherapy target. These data also support the feasibility of using these profiles for early detection of HCC.
一个世纪前,人们提出了宿主免疫系统的改变对癌症进展至关重要的观点,最近这一观点得到了实验支持。
本研究通过 Illumina 450K 平台对来自发现队列(健康对照组 = 69 例、慢性乙型肝炎患者 = 69 例和 HCC 患者 = 69 例)的外周血单个核细胞(PBMC)和 T 细胞进行 DNA 甲基化分析,检测肝癌(HCC)是否在宿主外周免疫系统中留下分子特征,并在两个验证队列(验证队列 1 = 80 例、验证队列 2 = 48 例)中使用焦磷酸测序进行验证。
本研究揭示了 HCC 在 PBMC 和 T 细胞 DNA 甲基化中的广泛特征,可将早期 HCC 与慢性乙型肝炎和丙型肝炎以及健康对照组区分开来,随着 HCC 的进展而增强,并且高度富集于免疫功能相关基因,如,这是当前癌症免疫治疗的靶点。这些数据还支持使用这些特征图谱进行 HCC 的早期检测。