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Classifier for predicting ICI drug application sensitivity of advanced tumor patients and application

A drug sensitivity, tumor patient technology, applied in the direction of instruments, biochemical equipment and methods, microbial determination/examination, etc.

Pending Publication Date: 2022-01-28
罗俊航 +4
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

At present, there is no report on predicting the sensitivity of advanced tumor patients to ICI drugs based on TMB

Method used

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  • Classifier for predicting ICI drug application sensitivity of advanced tumor patients and application
  • Classifier for predicting ICI drug application sensitivity of advanced tumor patients and application
  • Classifier for predicting ICI drug application sensitivity of advanced tumor patients and application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0012] Example 1 is used to predict the application of ICI class drug sensitivity classifier for patients with advanced tumors.

[0013] 1. Determination of TMB in patients with advanced tumors.

[0014] (1) Extract the DNA of the patient's tumor tissue and matched normal tissue.

[0015] (2) Perform high-throughput sequencing on the above samples.

[0016] (3) TMB is defined as the number of non-synonymous somatic mutations detected by sequencing per million bases. The TMB of the corresponding patient was calculated by the formula TMB=(number of somatic cells with non-synonymous mutations) / effective coverage area.

[0017] 2. Determination of the classifier threshold for predicting the sensitivity of advanced tumor patients to ICI drugs.

[0018] (1) The clinical data and TMB scores of 1661 patients who received ICI therapy were downloaded and analyzed from the cBioPortal database.

[0019] (3) The TMB scores for all samples ranged from 0 to 209.55 (median 5.90). For sum...

Embodiment 2

[0024] Example 2, the application of the classifier for predicting the sensitivity of advanced tumor patients to ICI drugs

[0025] Specifically, the classifier application method used to predict the sensitivity of ICI drugs in patients with advanced tumors is:

[0026] S1. Extract DNA from tumors and paired normal tissue samples of advanced cancer patients;

[0027] S2. Perform high-throughput sequencing on the above samples;

[0028] S3. Calculate the TMB score of the patient by the formula TMB=(number of somatic cells with non-synonymous mutations) / effective coverage area.

[0029] S4. Patients were divided into groups according to the classifier threshold (5.9). TMB higher than 5.9 was classified into the high TMB group, and vice versa into the low TMB group. In the high TMB group, the higher the TMB, the more sensitive the patients were to ICIs, and the OS improved more; in the low TMB group, the patients were less sensitive to ICIs.

[0030] S5. ICI drug therapy is re...

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Abstract

The invention discloses a classifier for predicting ICI drug application sensitivity of advanced tumor patients and application of the classifier. The target of predicting the sensitivity of the advanced tumor patients to the ICI drugs is achieved by detecting the tumor mutation burden (TMB) through sequencing and classifying the patients according to the classifier, the accuracy of defining the crowd of the advanced tumor patients applying the ICI drugs is improved, and the method has great significance in relieving the economic burden of the patients and prolonging the lifetime of the patients.

Description

technical field [0001] The invention relates to a classifier for predicting the sensitivity of advanced tumor patients to ICI drugs and its application, and relates to the definition of ICI drug-sensitive groups for predicting advanced tumor patients. Background technique [0002] Immune checkpoint inhibitor (ICI) therapy, including antibodies targeting programmed cell death protein 1 (PD-1), programmed death-ligand 1 (PD-1) -L1), cytotoxic T-lymphocyte-associated protein 4 (CTLA4), has revolutionized the treatment of patients with advanced tumors [1-5]. Although ICI drugs have brought new light to tumor treatment, only some patients are sensitive to ICI drugs during treatment [6-9]. In addition, ICI drugs are expensive, and the immune-related adverse reactions still need to be reduced [10-14], which brings troubles to the clinical use of ICI drugs. TMB is defined as non-synonymous somatic mutations detected by sequencing per million bases (including missense mutations, no...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12Q1/6886G16H50/30G06K9/62G06V10/764
CPCC12Q1/6886G16H50/30C12Q2600/156C12Q2600/106G06F18/241
Inventor 罗俊航陈炜韦锦焕潘绎晖
Owner 罗俊航
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