Abstract 956P
Background
Liver cancer is the third leading cause of cancer-related death worldwide and nearly half of deaths occur in China. The major histological types are hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). Serum marker alpha-fetoprotein (AFP) and ultrasound have been widely used in liver cancer high-risk population surveillance programs, but both methods have unsatisfactory sensitivities for early stage of the disease and sub-optimal specificities. AFP also has much lower sensitivity for ICC compared to HCC. Circulating tumor DNA (ctDNA) provides new opportunity for non-invasive detection of liver cancer. Here we intended to develop a blood-based liquid biopsy assay for liver cancer diagnosis by detecting abnormal methylation of cell-free DNA (cfDNA) as well as serum protein biomarkers.
Methods
Blood samples were collected from 333 liver cancer patients and 157 non-cancer age-matched control subjects (including 33 benign liver tumor patients, 105 liver cirrhosis patients, and 19 healthy individuals) in this multi-center study in China. cfDNA methylation and protein biomarker levels were analyzed.
Results
We identified a panel of 2 cfDNA methylation markers and 2 protein markers, AFP and des-gamma-carboxyprothrombin (DCP). Methylation markers were measured by quantitative real-time PCR and protein markers were measured by chemiluminescent enzyme immunoassay. We found that cfDNA methylation markers alone achieved a sensitivity of 81.3% for HCC and 88.1% for ICC, and a specificity of 92.4% in control samples. For BCLC stage 0-C HCC, the sensitivities were 58.8%, 70.9%, 94.6%, and 97.0%, respectively. When combined with AFP and DCP, overall sensitivities further improved to 96.6% for HCC and 86.2% for ICC. The integrated panel achieved sensitivities of 81.0%, 98.0%, 100.0%, and 97.5% for stage 0-C HCC respectively.
Conclusions
We developed a blood-based liquid biopsy with a panel of 2 cfDNA methylation markers and 2 protein markers for liver cancer diagnosis. It achieved high sensitivity for both HCC and ICC. The assay also showed high sensitivity for early stage HCC (stage 0 + A). These results highlighted the potential for multi-analyte liquid biopsy assay for early detection of liver cancer.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
1. Department of Liver Surgery & Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China 2. Envelope Health Biotechnology Co. Ltd., BGI-Shenzhen, Shenzhen, China.
Funding
Envelope Health Biotechnology Co. Ltd., BGI-Shenzhen, Shenzhen, China.
Disclosure
J. Sun: Financial Interests, Personal, Full or part-time Employment: Envelope Health Biotechnology Co. Ltd., BGI-Shenzhen. Y. Wang: Financial Interests, Personal, Full or part-time Employment: Envelope Health Biotechnology Co. Ltd., BGI-Shenzhen. R. Jiang: Financial Interests, Personal, Full or part-time Employment: Envelope Health Biotechnology Co. Ltd., BGI-Shenzhen. Z. Li: Financial Interests, Personal, Full or part-time Employment: Envelope Health Biotechnology Co. Ltd., BGI-Shenzhen. J. Peng: Financial Interests, Personal, Full or part-time Employment: Envelope Health Biotechnology Co. Ltd., BGI-Shenzhen. Z. Li: Financial Interests, Personal, Full or part-time Employment: Envelope Health Biotechnology Co. Ltd., BGI-Shenzhen. H. Chen: Financial Interests, Personal, Full or part-time Employment: Envelope Health Biotechnology Co. Ltd., BGI-Shenzhen. All other authors have declared no conflicts of interest.