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Human repeat element DNA methylation as markers for early diagnosis of liver cancer and application thereof

A technology of markers and methylation, which is applied in the direction of recombinant DNA technology, DNA/RNA fragments, microbial measurement/inspection, etc., can solve the problems of poor specificity, loss of radical resection, etc., and achieve high specificity and sensitivity.

Active Publication Date: 2019-05-31
TSINGHUA UNIV
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  • Summary
  • 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), many patients with liver cancer are often diagnosed at the middle and late stage, and the chance of radical resection is lost

Method used

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  • Human repeat element DNA methylation as markers for early diagnosis of liver cancer and application thereof
  • Human repeat element DNA methylation as markers for early diagnosis of liver cancer and application thereof
  • Human repeat element DNA methylation as markers for early diagnosis of liver cancer and application thereof

Examples

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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]The prototype sequences of human repetitive elements were downloaded from the Repbase database released by Gene Information Research Institute (GIRI), with a total of 583 prototype sequences and 31105 CpG sites. The bs-seeker2 software was ...

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 0.90, and the standard deviation of the accuracy rate is 0.11, 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 two...

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Abstract

The invention discloses an human repeat element DNA methylation as markers for early diagnosis of liver cancer and an application thereof.The invention belongs to the field of biological detection, and relates to markers for liver cancer and the application thereof.These markers are selected from one or more of the CpG sites modified at positions 64 on AluYg6,72,231 on AluSp,447,493,673 on L1HS,380,448 on L1,230 on AluYba3a2,1569 on LSAU, and 446 on LTR12E in Repbase data published by the Genetic Information Research Institute (GIRI).The invention further provides a system for diagnosing livercancer or predicting the risk of liver cancer by using the combination of the markers.The methylation states of the markers are obviously different in tumor tissues and non-tumor tissues; the methylation of the markers 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 90 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 human repetitive element DNA methylation as a marker for early diagnosis of liver cancer and its application. 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...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12Q1/6886C12N15/11
Inventor 汪小我张祥林方欢
Owner TSINGHUA UNIV
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