A high-throughput test enables specific detection of hepatocellular carcinoma

David Cheishvili (), Chifat Wong, Mohammad Mahbubul Karim, Mohammad Golam Kibria, Nusrat Jahan, Pappu Chandra Das, Md. Abul Khair Yousuf, Md. Atikul Islam, Dulal Chandra Das, Sheikh Mohammad Noor-E-Alam, Moshe Szyf, Sarwar Alam, Wasif A. Khan and Mamun Al Mahtab
Additional contact information
David Cheishvili: HKG Epitherapeutics Ltd. Unit 313-315, 3/F Biotech Center 2
Chifat Wong: HKG Epitherapeutics Ltd. Unit 313-315, 3/F Biotech Center 2
Mohammad Mahbubul Karim: International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR,B)
Mohammad Golam Kibria: International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR,B)
Nusrat Jahan: International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR,B)
Pappu Chandra Das: International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR,B)
Md. Abul Khair Yousuf: Bangabandhu Sheikh Mujib Medical University
Md. Atikul Islam: Bangabandhu Sheikh Mujib Medical University
Dulal Chandra Das: Bangabandhu Sheikh Mujib Medical University
Sheikh Mohammad Noor-E-Alam: Bangabandhu Sheikh Mujib Medical University
Moshe Szyf: McGill University
Sarwar Alam: Bangabandhu Sheikh Mujib Medical University
Wasif A. Khan: International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR,B)
Mamun Al Mahtab: Bangabandhu Sheikh Mujib Medical University

Nature Communications, 2023, vol. 14, issue 1, 1-16

Abstract: Abstract High-throughput tests for early cancer detection can revolutionize public health and reduce cancer morbidity and mortality. Here we show a DNA methylation signature for hepatocellular carcinoma (HCC) detection in liquid biopsies, distinct from normal tissues and blood profiles. We developed a classifier using four CpG sites, validated in TCGA HCC data. A single F12 gene CpG site effectively differentiates HCC samples from other blood samples, normal tissues, and non-HCC tumors in TCGA and GEO data repositories. The markers were validated in a separate plasma sample dataset from HCC patients and controls. We designed a high-throughput assay using next-generation sequencing and multiplexing techniques, analyzing plasma samples from 554 clinical study participants, including HCC patients, non-HCC cancers, chronic hepatitis B, and healthy controls. HCC detection sensitivity was 84.5% at 95% specificity and 0.94 AUC. Implementing this assay for high-risk individuals could significantly decrease HCC morbidity and mortality.

Date: 2023
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DOI: 10.1038/s41467-023-39055-7

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