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Nat Mater. 2017 Nov;16(11):1155-1161. doi: 10.1038/nmat4997. Epub 2017 Oct 9.

Circulating tumour DNA methylation markers for diagnosis and prognosis of hepatocellular carcinoma.

Author information

1
State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou 510060, China.
2
Moores Cancer Center and Institute for Genomic Medicine, University of California, San Diego, La Jolla, California 92093, USA.
3
Molecular Medicine Research Center, West China Hospital, Sichuan University, Chengdu 610041, China.
4
Guangzhou Youze Biological Pharmaceutical Technology Company Ltd., Guangzhou 510005, China.
5
Shanghai Center for Plant Stress Biology, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, Shanghai 210602, China.
6
Department of Clinical Laboratory Medicine, West China Hospital, Sichuan University, Chengdu 610041, China.
7
Department of Clinical Laboratory Medicine, Xijing Hospital, the Fourth Military Medical University, Xi'an, Shanxi 710032, China.
8
Veterans Administration Healthcare System, San Diego, California 92093, USA.

Abstract

An effective blood-based method for the diagnosis and prognosis of hepatocellular carcinoma (HCC) has not yet been developed. Circulating tumour DNA (ctDNA) carrying cancer-specific genetic and epigenetic aberrations may enable a noninvasive 'liquid biopsy' for diagnosis and monitoring of cancer. Here, we identified an HCC-specific methylation marker panel by comparing HCC tissue and normal blood leukocytes and showed that methylation profiles of HCC tumour DNA and matched plasma ctDNA are highly correlated. Using cfDNA samples from a large cohort of 1,098 HCC patients and 835 normal controls, we constructed a diagnostic prediction model that showed high diagnostic specificity and sensitivity (P < 0.001) and was highly correlated with tumour burden, treatment response, and stage. Additionally, we constructed a prognostic prediction model that effectively predicted prognosis and survival (P < 0.001). Together, these findings demonstrate in a large clinical cohort the utility of ctDNA methylation markers in the diagnosis, surveillance, and prognosis of HCC.

PMID:
29035356
DOI:
10.1038/nmat4997

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