Circulating tumor DNA detection system for screening minimal residual focus after colorectal cancer operation and predicting recurrence risk and application

A detection system and technology for colorectal cancer, applied in the field of circulating tumor DNA detection, can solve problems such as poor evaluation effect of risk stratification tools, inability to accurately guide adjuvant chemotherapy, difficulty in finding minimal residual lesions of colorectal cancer, and achieve recurrence prediction Risk, guiding postoperative adjuvant therapy, and the effect of convenient detection process

Active Publication Date: 2021-08-20
SUN YAT SEN UNIV CANCER CENT
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] The purpose of the present invention is to solve the problem that the existing risk stratification tools for colorectal cancer patients after radical resection are not effective in evaluating, it is difficult to find small residual lesions after radical resection of colorectal cancer, and it is impossible to accurately guide adjuvant chemotherapy. Detecting deficiencies of ctDNA technology

Method used

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  • Circulating tumor DNA detection system for screening minimal residual focus after colorectal cancer operation and predicting recurrence risk and application
  • Circulating tumor DNA detection system for screening minimal residual focus after colorectal cancer operation and predicting recurrence risk and application
  • Circulating tumor DNA detection system for screening minimal residual focus after colorectal cancer operation and predicting recurrence risk and application

Examples

Experimental program
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Effect test

Embodiment 1

[0041] Example 1: Detection of circulating tumor DNA

[0042] 1. Sample source: 240 colorectal cancer patients who underwent radical surgery were treated and followed up regularly according to current guidelines.

[0043] 2. Sample collection: collect tumor tissue samples and peripheral blood leukocyte samples from patients after surgery, 3-7 days after surgery, 6 months after surgery, 9 months after surgery, 12 months after surgery, 15 months after surgery, After 18 months, 21 months, and 24 months after surgery, plasma samples were taken continuously from the patients.

[0044] 3. Detection method:

[0045] 1. High-throughput sequencing: Obtain surgically resected tumor tissue samples and peripheral blood leukocyte samples from patients with colorectal cancer, extract genomic DNA from the cells, construct sequencing libraries, and then use the next-generation sequencing gene assembly panel containing 425 cancer-related genes ( panel) for targeted capture, the specific gene...

Embodiment 2

[0065] Example 2: Continuous blood sampling to detect circulating tumor DNA and identify tumor recurrence

[0066] Based on Example 1, colorectal cancer patients with continuous postoperative plasma samples (≥3) and sufficient follow-up time (≥24 months or tumor recurrence) were included to analyze whether continuous blood sampling to detect circulating tumor DNA can identify tumor recurrence early.

[0067] Follow up to observe whether the ctDNA-positive patients determined by the detection system of the present invention have tumor recurrence in the end, and calculate the time from the first ctDNA test being positive to tumor recurrence, which is the advance of ctDNA detection in predicting tumor recurrence compared with conventional imaging methods time.

[0068] Such as figure 2 As shown in A, the parameters of the COX proportional hazard model calculated based on the follow-up survival data of the patient are: hazard ratio ln[h(t,X) / h 0 (t)]=32.02*ctDNA, patients with ...

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Abstract

The invention relates to a circulating tumor DNA detection system for screening existence of postoperative minimal residual focuses of colorectal cancer patients and predicting recurrence risk. The detection system comprises a colorectal cancer tissue gene mutation screening module, a plasma free DNA gene mutation analysis module and a circulating tumor DNA state judgment module. The system utilizes the same next-generation sequencing gene combination panel to detect primary tumor tissue and plasma free DNA, and considers all mutations detected in the primary tumor tissue of a patient instead of being limited to individual gene mutations, so that the system is more comprehensive. The system can be applied to dynamic and real-time monitoring of circulating tumor DNA, and can be used for evaluating the residual condition of minimal residual lesions after colorectal cancer radical operation, predicting the recurrence risk and guiding the postoperative treatment decision.

Description

technical field [0001] The invention belongs to the technical field of tumor prognosis assessment, and in particular relates to the detection and application of circulating tumor DNA. Background technique [0002] Colorectal cancer is the third most common cancer worldwide, with more than 19 million new cases each year. Colorectal cancer is also the second leading cause of cancer-related death, with a five-year mortality rate of approximately 40%. Through screening based on serum carcinoembryonic antigen and colonoscopy, more and more patients can be diagnosed before distant metastases, for which surgical resection is the best treatment. However, a considerable number of patients still relapse after radical resection. Minimal residual disease (Minimal residual disease, MRD) is considered to be the main source of disease recurrence, but the minimal residual disease is often not visible on imaging, therefore, it is widely used clinically to "has clinicopathological high-risk...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): G16B20/50C12Q1/6869C12Q1/6886G16B20/30
CPCG16B20/50G16B20/30C12Q1/6886C12Q1/6869C12Q2600/156C12Q2535/122
Inventor 徐瑞华王峰陈功邵阳
Owner SUN YAT SEN UNIV CANCER CENT
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