Noninvasive human liver cancer early detection and differential diagnosis method and system

A technology for early detection and differential diagnosis, applied in the field of clinical medicine, can solve the problems of imaging examinations that cannot be used for early diagnosis, serological tests lack specificity, and cannot be used for early diagnosis.

Inactive Publication Date: 2015-01-28
YIKONGENOMICS
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Problems solved by technology

Serological tests often lack specificity, and imaging tests sometimes cannot be used for early diagnosis or qual

Method used

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  • Noninvasive human liver cancer early detection and differential diagnosis method and system
  • Noninvasive human liver cancer early detection and differential diagnosis method and system
  • Noninvasive human liver cancer early detection and differential diagnosis method and system

Examples

Experimental program
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Effect test

Embodiment 1

[0023] Example 1: Genome CNV analysis of cell-free peripheral blood DNA

[0024] The isolated plasma of 31 cases of clinically diagnosed liver cancer patients and 8 cases of isolated plasma of patients with chronic hepatitis and cirrhosis were collected, and the free DNA in the plasma was extracted, and the genome sequencing library was constructed with the kit of NEB Company. The DNA of each library was initially The dosage is 3-5ng. The Illumina Hiseq2500SR41 method was used for genomic DNA sequencing, and the effective sequencing number of each sample was 10M. BWA software was used for sequence comparison, and then CNV analysis was performed according to the steps of the present invention, wherein the CNV normal control data used came from 250 normal people.

[0025] As a result of the measurement, it was found that some liver cancer patients (41.9%, 13 / 31) had observed abnormal changes in the chromosome CNV map, and the chronic hepatitis and liver cirrhosis group had no v...

Embodiment 2

[0026] Embodiment 2: the establishment of Z-score CNV comprehensive scoring method

[0027] Score according to the following principles: 4 points for visually observable copy number changes on the chromosome CNV map, 2 points for 1q, 7q, or 19q copy number increase in the above-mentioned Z-score CNV changes, and 2 points for the above-mentioned 1p, 9q, or 14q CNV changes The copy number reduction is 0.5 points, and 1.5 is the critical value, higher than or equal to 1.5 is high risk of liver cancer, and less than 1.5 is low risk of liver cancer.

[0028] The high risk of liver cancer indicates that the possibility of liver cancer is high, especially on the basis of chronic hepatitis and cirrhosis. It is necessary to follow closely and use other methods to verify the existence of liver cancer, so as to achieve the purpose of early diagnosis and early treatment. The CNV composite score is correlated with the size of liver cancer, see figure 2 .

Embodiment 3

[0029] Example 3: Application of CNV Comprehensive Score in Early Detection and Differential Diagnosis of Liver Cancer

[0030] The above-mentioned CNV comprehensive scoring method analyzes liver cancer and chronic hepatitis liver cirrhosis measurement data, and the positive rate of the liver cancer group is 83.9% (26 / 31), the positive rate of the liver cancer group below 50mm is 68.8% (11 / 16), and the positive rate of the liver cancer group below 30mm The positive rate was 57.1% (4 / 7), the positive rate was 70% (7 / 10) in the liver cancer group with negative serum AFP or lower level (less than 50ng / ml), and all negative in the hepatitis cirrhosis group (0 / 8 ), the overall sensitivity was 84%, and the specificity was 100%. ROC plot see image 3 .

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Abstract

The invention discloses a noninvasive human liver cancer early detection and differential diagnosis method which comprises the following steps: 1) extracting free DNA of plasma from in-vitro plasma, and constructing a genomic sequencing library; 2) sequencing the DNA, measuring the DNA sequence of the genome, and performing sequence alignment; 3) by taking different genome sequence lengths as basic analysis units, performing chromosome copy number variation CNV analysis, and constructing chromosome CNV graphs to observe whether visual observable copy number variation exists; and 4) by taking the different genome sequence lengths as basic analysis units, performing Z-score analysis of chromosome copy number variation CNV. The detection method disclosed by the invention can be used for early detection and differential diagnosis of liver cancer and is used for preclinical study or clinical detection.

Description

technical field [0001] The invention relates to a molecular detection method for realizing non-invasive early detection and differential diagnosis of liver cancer by detecting isolated blood, and belongs to the field of clinical medicine. Background technique [0002] Liver cancer is the fifth most common cancer and the second most common cause of cancer death in the world. The survival rate of small liver cancer after surgery can reach more than 80%, but most patients are diagnosed at an advanced stage, and the survival rate is often less than 6 months. Therefore, timely and accurate diagnosis of liver cancer is the primary task to improve the survival rate of liver cancer patients. Because liver cancer often occurs on the basis of chronic hepatitis cirrhosis, it is generally not easy to distinguish early. Therefore, traditional detection methods have many defects in the early detection, differential diagnosis and early treatment of liver cancer, especially the inability to...

Claims

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Application Information

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IPC IPC(8): C12Q1/68C40B50/06
CPCC12Q1/6869C40B50/06
Inventor 朱克卿邢同京徐洪涛徐祖龙朱霞胡月薄世平陆思嘉王春香
Owner YIKONGENOMICS
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