Methods for determining the risk of developing hepatocellular carcinoma from nonalcoholic steatohepatitis

By employing DNA methylation analysis to assess specific CpG sites in liver tissue, this method effectively predicts the risk of hepatocellular carcinoma in NASH patients, addressing the limitations of current diagnostic approaches and enabling early intervention.

JP7681904B2Active Publication Date: 2025-05-23KEIO UNIV
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Patent Information

Application Number
JP2021564004
Authority / Receiving Office
JP · JP
Patent Type
Patents
Current Assignee / Owner
Priority Date
2019-12-09
Filing Date
2020-12-09
Publication Date
2025-05-23
Estimated Expiration
2040-12-09

AI Technical Summary

Technical Problem

There is a growing need for an effective method to predict the risk of developing hepatocellular carcinoma from non-alcoholic steatohepatitis (NASH), as current diagnostic methods are invasive, costly, and not suitable for early detection.

Method used

A method involving DNA methylation analysis to detect the risk of hepatocellular carcinoma in patients with NASH by measuring the methylation levels of specific CpG sites in liver tissue, using bisulfite-treated genomic DNA and advanced detection techniques such as Infinium assays or HPLC.

Benefits of technology

This method enables early and accurate identification of NASH patients at high risk of developing hepatocellular carcinoma, facilitating timely intervention and improving treatment outcomes.

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Abstract

Provided is a method for assessing the risk of developing hepatocellular carcinoma from nonalcoholic steatohepatitis (NASH). A method for detecting hepatocytes having a risk of developing hepatocellular carcinoma or detecting tissue that contains said hepatocytes, wherein the method includes detecting the DNA methylation level of target CpG sites in genomic DNA derived from hepatocytes affected with NASH or from tissue that contains said hepatocytes, and detecting hepatocytes having the risk of developing hepatocellular carcinoma or tissue that contains said hepatocytes from the detected DNA methylation level.
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Claims

1. A method for detecting hepatocytes or tissues containing hepatocytes at risk of developing hepatocellular carcinoma, comprising: Detecting the DNA methylation level of a target CpG site in genomic DNA derived from a liver cell or a tissue containing the liver cell affected with nonalcoholic steatohepatitis; and Detecting hepatocytes or tissues containing hepatocytes at risk of developing hepatocellular carcinoma based on the detected DNA methylation level; Including, The target CpG site is at least one CpG site selected from the group consisting of CpG sites at chromosomal positions listed in Table 1 and CpG sites located in a region 20 bases upstream to 20 bases downstream from each of the positions; method. 【Table 1】

2. 1. A method for detecting a subject at risk for developing hepatocellular carcinoma, comprising: Detecting the DNA methylation level of a target CpG site in genomic DNA derived from a liver cell or a tissue containing the liver cell of a subject suffering from non-alcoholic steatohepatitis; and Detecting a subject at risk of developing hepatocellular carcinoma from the detected DNA methylation level; Including, The target CpG site is at least one CpG site selected from the group consisting of CpG sites at chromosomal positions listed in Table 2 and CpG sites located in a region 20 bases upstream to 20 bases downstream from each of the positions; method. 【Table 2】

3. A method for obtaining data for detecting hepatocytes or tissues containing the same at risk of developing hepatocellular carcinoma, or subjects at risk of developing hepatocellular carcinoma, comprising the steps of: Detecting the DNA methylation level of a target CpG site in genomic DNA derived from a liver cell or a tissue containing the liver cell of a subject suffering from non-alcoholic steatohepatitis; and Obtaining data on whether or not the hepatocyte or a tissue containing the hepatocyte, or the subject, is at risk of developing hepatocellular carcinoma from the detected DNA methylation level; Including, The target CpG site is at least one CpG site selected from the group consisting of CpG sites at chromosomal positions listed in Table 3 and CpG sites located in a region 20 bases upstream to 20 bases downstream from each of the positions; method. 【Table 3】

4. The method according to any one of claims 1 to 3, wherein the target CpG site is at least one CpG site selected from the group consisting of the CpG sites at positions 130,834,003 on chromosome 10, 114,256,392 on chromosome 2, 28,829,182 on chromosome 6, 144,601,781 on chromosome 8, 144,601,800 on chromosome 8, and 35,700,382 on chromosome 6, and CpG sites located in a region 20 bases upstream to 20 bases downstream from each of said positions.

5. The method according to any one of claims 1 to 4, wherein the detection of the DNA methylation level comprises detecting the DNA methylation level of the target CpG site using the genomic DNA that has been bisulfite-treated.

Citation Information

Patent Citations

  • Novel methylation site regulating expression of MDA-9 / syntenin

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