Method and system for evaluating colorectal cancer metastasis and recurrence risk and dynamically monitoring based on methyl marker combination

A colorectal cancer and risk monitoring technology, applied in the field of bioinformatics, can solve problems such as poor sensitivity and stability, and achieve the effects of improving survival rate and quality of life, improving usability, and excellent sensitivity

Pending Publication Date: 2021-06-18
SOUTHERN MEDICAL UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, most of the current studies on ctDNA methylation are based on quantitative analysis of methylation of a single gene or several genes by methylation-specific PCR or digital PCR, which has poor sensitivity and stability.

Method used

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  • Method and system for evaluating colorectal cancer metastasis and recurrence risk and dynamically monitoring based on methyl marker combination
  • Method and system for evaluating colorectal cancer metastasis and recurrence risk and dynamically monitoring based on methyl marker combination
  • Method and system for evaluating colorectal cancer metastasis and recurrence risk and dynamically monitoring based on methyl marker combination

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Experimental program
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Embodiment 1

[0054] The collection of embodiment 1 tissue and plasma sample:

[0055] (1) 191 formalin-fixed and paraffin embedded tissues (Formaldehyde-fixed and paraffin embedded tissues, FFEP) samples and 263 plasma samples were collected from the Department of Pathology and General Surgery of Southern Hospital and Southern Theater General Hospital.

[0056] FFEP tissue: 52 cases of normal intestinal mucosa (outer intestinal mucosa >1cm around the tumor) and 138 cases of colorectal cancer tissue (27 cases of stage I, 30 cases of stage II, 33 cases of stage III, 35 cases of primary tumor of stage IV, 35 cases of primary tumor of stage IV 40 cases of distant metastases); Among them, 25 cases of paired samples of stage IV primary tumors and metastases. There were 86 male patients and 53 female patients, with an average age of 58 (25-79 years old). Select a tissue block with tumor tissue accounting for more than 30%, slice the thickness of 5-6 μm, cut 6-8 slices, remove the slice and stick...

Embodiment 2

[0061] Embodiment 2 bisulfite conversion

[0062] Sulphite Conversion Sulphite conversion was performed according to the instructions of the EZ DNA Methylation Modification Kit ((Cat#D5031, Zymo Research).

Embodiment 3

[0063] Example 3 Baseline Medical IRIS TM Targeted Methylation Sequencing

[0064] Anchor IRIS TM Pre-library construction using Anchor Dx EpiVisio TM Methylation Pre-Library Construction Kit (Anchor Dx, Cat#A0UX00019) and EpiVisio TM The indexing PCR kit (Anchor Dx, Cat#A2DX00025) was used for pre-library construction. Subsequent purification of the amplified pre-library using IPB1 magnetic beads, Qubit TM The dsDNA HS assay kit detects the pre-library concentration. If the DNA content in the pre-library exceeds 400ng, further targeted enrichment can be performed.

[0065] Anchor IRIS TM Target Enrichment Benchmark Medical Company EpiVision TM The Targeted DNA Enrichment Kit (AnchorDx, Cat#A0UX00031) performs efficient liquid-phase capture of the DNA in the pre-library to enrich the targeted region. A 10K methylation panel containing 9921 cancer-specific methylated preselected regions was selected to obtain the enriched final library. The 10K panel is based on the ...

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Abstract

The invention relates to a method and a system for evaluating colorectal cancer metastasis and recurrence risk and dynamically monitoring based on a methyl marker combination, and particularly discloses a colorectal cancer metastasis and recurrence risk monitoring method. The method comprises the following steps: S1) forming a training set database; S2) training data in the training set database by adopting a random forest model to obtain a mapping relationship between a methylation signal value of a ctDNA methylation block of a plasma sample of a colorectal cancer patient and non-recurrence lifetime information of a corresponding sample and a correlation model; S3) taking a methylation signal value of a ctDNA methylation block of a patient to be predicted as an input value, and predicting the recurrence progress risk of the patient through the correlation model. The prediction model can noninvasively, sensitively and quickly predict the progress of CRC, the progress risk monitoring after the radical treatment of CRC patients is realized, the clinical optimization treatment scheme is guided, and the survival rate and life quality of the patients are improved.

Description

technical field [0001] The invention belongs to the field of bioinformatics, and in particular relates to a method and system for assessing the risk of metastasis and recurrence of colorectal cancer and dynamic monitoring based on a combination of methyl markers. Background technique [0002] The main cause of death in patients with colorectal cancer (CRC) is tumor recurrence and metastasis [1]. Currently, the main treatment for stage III CRC is radical tumor resection adjuvanted with chemotherapy based on CapeOX (capecitabine + oxaliplatin) or FOLFOX (oxaliplatin, fluorouracil, and leucovorin). About 30%-50% of the later CRC patients relapsed [2-3]. If the risk prediction and timely adjustment of treatment options (such as secondary surgical resection, targeted therapy or immunotherapy) can be performed for patients who do not benefit from these comprehensive treatments or who have progressed, it is expected to improve the overall survival rate and quality of life of patie...

Claims

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Application Information

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IPC IPC(8): G16H50/30G16B20/30G06N3/08G06K9/62C12Q1/6886
CPCG16H50/30G16B20/30C12Q1/6886G06N3/088C12Q2600/154G06F18/23G06F18/24323
Inventor 梁莉王蔚蓝孝亮丁彦青张学聪
Owner SOUTHERN MEDICAL UNIVERSITY
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