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Superficial modification based 5hmC (5-hydroxymethylcytosine) polymolecular marker and CRC (colorectal cancer) early diagnosis model

A colorectal cancer, diagnostic model technology, applied in the field of clinical biomedicine, to achieve the effect of convenient detection, strong stability, and improved compliance

Active Publication Date: 2019-03-22
ZHONGSHAN HOSPITAL FUDAN UNIV
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

In the prior art, there is no report about the 5hmC multimolecular marker and early diagnosis model of colorectal cancer based on the appearance modification of the present invention

Method used

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  • Superficial modification based 5hmC (5-hydroxymethylcytosine) polymolecular marker and CRC (colorectal cancer) early diagnosis model
  • Superficial modification based 5hmC (5-hydroxymethylcytosine) polymolecular marker and CRC (colorectal cancer) early diagnosis model
  • Superficial modification based 5hmC (5-hydroxymethylcytosine) polymolecular marker and CRC (colorectal cancer) early diagnosis model

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Embodiment 1

[0059] Embodiment 1 Construction of colorectal cancer early diagnosis model

[0060] 1. Screening of genetic markers

[0061] The present invention enrolls 100 patients with stage I-III colorectal cancer and 100 healthy people with normal colonoscopic examination. With informed consent, 10ml of peripheral venous blood was collected for testing. The detection process cooperates with Shanghai Yibien Gene Technology Co., Ltd., and adopts the 5-hmC sequencing (Nano-hmC-Seal) technology with low input DNA. The detection process is as follows: figure 1 shown. The 5-hmC expression level of more than 20,000 gene loci in the whole genome was detected. Such as figure 2 As shown in (left), there is no significant difference in PCI dimensionality reduction in the whole genome 5-hmC expression between the two groups. Then, we used the Deseq method to compare the differences in 5-hmC expression at each gene locus between the two groups, and selected the top 80 genes with the largest di...

Embodiment 2

[0077] Embodiment 2 Verification of early diagnosis model of colorectal cancer

[0078] Internal validation of the constructed diagnostic model. Using the model constructed in Example 1 to score 200 samples, the cutoff value is 0.5, and the result is greater than or equal to 0.5 to be diagnosed as colorectal cancer, otherwise it is considered a healthy person, and the judgment result is as follows Figure 4 (left) shown. Among 100 colorectal cancer patients, 92 cases were diagnosed as colorectal cancer, and 8 cases were misjudged; among 100 healthy people, 90 cases were judged as non-colorectal cancer, and 10 cases were misjudged. The sensitivity and specificity of internal validation were 92% and 90%. The area under the AUC curve of the internal validation is 0.9488, and the sensitivity and specificity values ​​are 89.4% and 93.4% respectively, see Figure 4 (right).

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Abstract

The invention relates to the technical field of clinical molecular diagnosis, in particular to a superficial modification based 5hmC (5-hydroxymethylcytosine) polymolecular marker and a CRC (colorectal cancer) early diagnosis model. With the adoption of a 5-hmC high throughput sequencing technology, 5-hmC expression quantities of peripheral blood plasma DNA whole genomes of a CRC patient and a healthy person are checked, 5-hmC differential expression of genetic loci of the whole genomes of the two groups of samples are compared, the genetic locus of the part with the most obvious differentialexpression is screened as the gene marker of the diagnosis model, and then the CRC early diagnosis model is constructed. Verification proves that the diagnosis sensitivity and specificity are both higher, and compared with a stool occult blood detection kit and a spetin9 kit in the market currently, sensitivity and specificity are improved by about 20% and 8% respectively. The diagnosis method hasthe advantages of being noninvasive in detection and convenient, can be applied to the first-line clinic and is used for early screening of CRC.

Description

technical field [0001] The invention relates to the technical field of clinical biomedicine, in particular to a 5hmC multimolecular marker based on appearance modification and an early diagnosis model of colorectal cancer. Background technique [0002] Colorectal cancer (CRC) is one of the most common malignant tumors of the digestive tract, and the incidence and mortality of colorectal cancer rank third among malignant tumors worldwide. The situation in my country is similar. Colorectal cancer is the fifth malignant tumor in male and the fourth female in terms of mortality. And due to the anatomical characteristics of colorectal venous reflux, about 25% of patients have liver metastases at the time of treatment, which significantly reduces the 5-year survival rate of colorectal cancer patients. The 5-year survival rate of patients diagnosed and treated at the early stage of colorectal cancer is significantly higher than that of stage IV patients. Therefore, diagnosis at t...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12Q1/6886G16H50/20
CPCC12Q1/6886C12Q2600/158G16H50/20
Inventor 许剑民常文举刘天宇韦烨任黎何国栋吉美玲朱德祥陈竟文冯青阳
Owner ZHONGSHAN HOSPITAL FUDAN UNIV
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