A high-throughput test enables specific detection of hepatocellular carcinoma

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.

Comprehensive pan-cancer analysis of cfDNA methylation marks in tumors reveals complex epigenetic regulatory circuits and diagnostic biomarkers

“…Liquid biopsy tests can detect cancer in some cases several years before clinical signs and symptoms occur 49 , and single methylation sites in liquid biopsies can explicitly detect cancer 50 . However, such tests have not been developed into routinely applicable tools, partly because of di culties in assay design for bisul te-treated DNA and due to challenges in speci city and in processing high throughput DNA methylation data.…”

Genetic screening of liver cancer: State of the art

“…This diagnostic prediction model showed high specificity and sensitivity, but if there is DNA contamination, it can potentially yield false positives. To address this challenge, Cheishvili et al [ 88 ] used over 12000 methylation profiles in The Cancer Genome Atlas ( ) and the Gene Expression Omnibus data repository collections ( )[ 88 ]. They determined the DNA methylation sites, which are consistently unmethylated in all blood DNA and tissue samples.…”

Co-Reactive Ligand In Situ Engineered Gold Nanoclusters with Ultra-Bright Near-Infrared Electrochemiluminescence for Ultrasensitive and Label-Free Detection of Carboxylesterase Activity

“…Hepatocellular carcinoma (HCC), as the most common type of primary liver cancer, has a terrible survival rate (<5% during 5 years) owing to the overwhelming number of patients that are diagnosed late, leading to terrible treatment. 1,2 A noninvasive and accurate diagnosis of HCC undoubtedly holds crucial promise in improving patient survival. Although alpha-fetoprotein (AFP) is a typical serologic biomarker for HCC in early diagnosis, the detection of AFP cannot efficiently distinguish HCC from other liver diseases because of limited sensitivity or specificity.…”

“…Hepatocellular carcinoma (HCC), as the most common type of primary liver cancer, has a terrible survival rate (<5% during 5 years) owing to the overwhelming number of patients that are diagnosed late, leading to terrible treatment. , A noninvasive and accurate diagnosis of HCC undoubtedly holds crucial promise in improving patient survival. Although alpha-fetoprotein (AFP) is a typical serologic biomarker for HCC in early diagnosis, the detection of AFP cannot efficiently distinguish HCC from other liver diseases because of limited sensitivity or specificity. , Fortunately, carboxylesterase (CE) (EC 3.1.1.1), one of the most abundant serine hydrolases responsible for the metabolism of various xenobiotics in the human liver, could serve as an efficient serological biomarker candidate for HCC because the difference between HCC and liver cirrhosis is significant compared to that with AFP. , Currently, commercial kits have been used to determine CE activity with a colorimetric assay, which suffers from a relatively low sensitivity.…”