epiLiver a novel tumor specific, high throughput and cost-effective blood test for specific detection of liver cancer (HCC)
Robust cost effective and high-throughput tests for early detection of cancer in otherwise healthy people could potentially revolutionize public-health and the heavy personal and public burden of the morbidity and mortality from cancer. Several studies have delineated tumor specific DNA methylation profiles that could serve as biomarkers for early detection of Hepatocellular Carcinoma (HCC) as well as other cancers in liquid biopsies. Several published DNA methylation markers fail to distinguish HCC DNA from DNA from other tissues and other cancers that are potentially present in plasma. We describe a set of DNA methylation signatures in HCC that are “categorically” distinct from normal tissues and blood DNA methylation profiles. We develop a classifier combined of 4 CG sites that is sufficient to detect HCC in TCGA HCC data set at high accuracy. A single CG site at the F12 gene is sufficient to differentiate HCC samples from thousands of other blood samples, normal tissues and 31 tumors in the TCGA and Gene Expression Omnibus (GEO) data repository (n = 11,704). A “next generation sequencing”-targeted-multiplexed high-throughput assay was developed, which was used to examine in a clinical study plasma samples from HCC, chronic hepatitis B (CHB) patients and healthy controls (n = 398). The sensitivity for HCC detection was 84.5% at a specificity of 95% and AUC of 0.94. Applying this assay for routine follow up of people who are at high risk for developing HCC could have a significant impact on reducing the morbidity and mortality from HCC.
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This is a list of supplementary files associated with this preprint. Click to download.
Table S1. Model statistics for “HCC-detect”.
Table S2. List number of samples and acronyms of other cancers analyzed.
Table S3. Model statistics for “HCC-spec”.
Table S4. ROCs for “HCC-detect” sum “HCC-spec” + “HCC-detect” sum scores and number of samples with methylation values larger than 0.2.
Fig. S1. Differential methylation of “HCC-detect” and “HCC-spec” CGs at different stages of HCC in the Dhaka clinical study. Mean methylation and confidence intervals for the 4 CGs included in the “HCC-detect” set (cg02012576 (CHFR), cg03768777 (VASH2), cg05739190 (CCNJ), cg24804544 (GRID2IP) and “HCC-spec” cg14126493 (F12) (n for each group as indicated in Fig. 5). B. heat map depicting the methylation values for all CGs that were included in the sequenced regions for all 5 genes.
Posted 23 Feb, 2021
epiLiver a novel tumor specific, high throughput and cost-effective blood test for specific detection of liver cancer (HCC)
Posted 23 Feb, 2021
Robust cost effective and high-throughput tests for early detection of cancer in otherwise healthy people could potentially revolutionize public-health and the heavy personal and public burden of the morbidity and mortality from cancer. Several studies have delineated tumor specific DNA methylation profiles that could serve as biomarkers for early detection of Hepatocellular Carcinoma (HCC) as well as other cancers in liquid biopsies. Several published DNA methylation markers fail to distinguish HCC DNA from DNA from other tissues and other cancers that are potentially present in plasma. We describe a set of DNA methylation signatures in HCC that are “categorically” distinct from normal tissues and blood DNA methylation profiles. We develop a classifier combined of 4 CG sites that is sufficient to detect HCC in TCGA HCC data set at high accuracy. A single CG site at the F12 gene is sufficient to differentiate HCC samples from thousands of other blood samples, normal tissues and 31 tumors in the TCGA and Gene Expression Omnibus (GEO) data repository (n = 11,704). A “next generation sequencing”-targeted-multiplexed high-throughput assay was developed, which was used to examine in a clinical study plasma samples from HCC, chronic hepatitis B (CHB) patients and healthy controls (n = 398). The sensitivity for HCC detection was 84.5% at a specificity of 95% and AUC of 0.94. Applying this assay for routine follow up of people who are at high risk for developing HCC could have a significant impact on reducing the morbidity and mortality from HCC.
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