DNA methylation markers for diagnosing early liver cancer by using peripheral blood and application thereof

A marker and methylation technology, applied in recombinant DNA technology, DNA/RNA fragment, microbial determination/inspection, etc., can solve the problems of poor specificity, loss of radical resection, etc., and achieve the effect of high specificity and sensitivity

Active Publication Date: 2019-05-31
TSINGHUA UNIV
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] Liver cancer is a common malignant tumor. Due to the poor specificity of existing markers (such as alpha-fetoprotein),

Method used

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  • DNA methylation markers for diagnosing early liver cancer by using peripheral blood and application thereof
  • DNA methylation markers for diagnosing early liver cancer by using peripheral blood and application thereof
  • DNA methylation markers for diagnosing early liver cancer by using peripheral blood and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0051] Example 1 Genome-wide methylation sequencing data screening of differential CpG sites on ribosomal DNA

[0052] We used peripheral blood bisulfite sequencing data published in PNAS titled "Noninvasive detection of cancer-associated genome-wide hypomethylation and copy number aberrations by plasmaDNA bisulfite sequencing" in 2013, and the data were deposited in the European Genome-Table Phenome Archives (European Genome-Phenome Archive), accession number is EGAS00001000566. Here we use the peripheral blood DNA methylation data of healthy people (32), HBV-infected non-cancer patients (8), early liver cancer patients (stage I, stage II, 26), and 15 pairs of liver cancer tissues and white blood cells Layer DNA methylation data.

[0053] Download the reference sequence U13369.1 of the human ribosomal DNA repeat fragment unit in GENBANK, with a total length of 42999 bases and 3288 CpG sites. Use the bs-seeker2 software to match the sequencing data back to U13369.1 on the re...

Embodiment 2

[0064] Embodiment 2 test concentrates the effect of test marker

[0065] In the 100 random splits of the training set and the test set, the regularized logistic model was trained using the training set, the model was applied to the test set, and the accuracy in the test set was calculated. Figure 4 A boxplot of the accuracy of the model on the test set is given for 100 random splits of the dataset. The average accuracy rate is 0.9513, and the standard deviation of the accuracy rate is 0.0686, indicating that a very good discrimination effect has been achieved.

[0066] Herein, the terms "first" and "second" are only used for descriptive purposes, and cannot be understood as indicating or implying relative importance or implicitly specifying the quantity of indicated technical features. Thus, the features defined as "first" and "second" may explicitly or implicitly include at least one of these features. In the description of the present invention, "plurality" means at least...

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Abstract

The invention discloses DNA methylation markers for diagnosing early liver cancer by using peripheral blood and an application thereof.The invention belongs to the field of biological detection, and relates to the markers for liver cancer and the application thereof, wherein the markers include at least one CpG site selected from the group consisting of CpG sites or modified CpG sites at positions24167,36996,37361,37178,39913,30789,37020,36832,34428, or 34805based on the human ribosomal DNA repeat fragment unit reference sequence U13369.1.The invention further provides a system, a kit and thelike for diagnosing the liver cancer by using the combination of the markers.The methylation state of the markers is obviously different in tumor tissues and non-tumor tissues; the methylation of themarkers is low in the tumor tissues, and the accuracy rate of distinguishing whether or not a patient suffers from liver cancer in a test set by the marker combination reaches 95 percent.

Description

technical field [0001] The invention belongs to the field of biological detection, and relates to a marker for liver cancer and its application, in particular to a DNA methylation marker and its application for diagnosing early liver cancer by peripheral blood. Background technique [0002] Detection of diseases in peripheral blood is a minimally invasive or even non-invasive detection method. There are free DNA in peripheral blood, and these free DNA comes from the DNA released into the blood by apoptosis. Therefore, some problems in the body can be identified through the analysis of free DNA. [0003] DNA methylation is an important part of epigenetics, and DNA methylation plays a vital role in gene regulation. Existing studies have shown that the occurrence of cancer is very closely related to genomic DNA methylation, which makes it a reality to detect cancer by identifying the variation of DNA methylation. DNA methylation refers to the process of transferring a methyl ...

Claims

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Application Information

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IPC IPC(8): C12Q1/6886C12N15/11
Inventor 汪小我张祥林方欢李衍达
Owner TSINGHUA UNIV
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