Application of flt3 gene mutation in predicting sensitivity to immune checkpoint inhibitor therapy in patients with non-small cell lung cancer

A non-small cell lung cancer, immune checkpoint technology, applied in the field of clinical molecular diagnostics, can solve the problem of not covering people who benefit from immunotherapy, and achieve the effect of avoiding blind medication, improving detection efficiency, and simplifying detection content.

Active Publication Date: 2022-01-21
NANJING SIMCERE MEDICAL LAB CO LTD +2
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the above gene mutations as biomarkers still cannot cover all potential immunotherapy benefit populations, and there is still a need in the field to more efficiently and accurately identify methods and tools suitable for immune checkpoint inhibitors to treat lung cancer patients

Method used

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  • Application of flt3 gene mutation in predicting sensitivity to immune checkpoint inhibitor therapy in patients with non-small cell lung cancer
  • Application of flt3 gene mutation in predicting sensitivity to immune checkpoint inhibitor therapy in patients with non-small cell lung cancer
  • Application of flt3 gene mutation in predicting sensitivity to immune checkpoint inhibitor therapy in patients with non-small cell lung cancer

Examples

Experimental program
Comparison scheme
Effect test

Embodiment

[0073] The present invention specifically adopts following methodology to study

[0074] Sample material: Experimental samples were obtained from FFPE tumor samples of Chinese non-small cell lung cancer patients and paired peripheral whole blood control samples (all patients provided written informed consent). The study was analyzed by targeted capture NGS sequencing, specifically involving a panel comprising 551 cancer-associated genes.

[0075] experiment method:

[0076] 1) The present invention uses a finished commercial kit to extract the DNA of FFPE slices and whole blood samples with tumor cells accounting for more than 20%, and the extracted nucleic acid is quantified by Qubit and analyzed by Aglient 2100 before entering the library construction.

[0077] Specifically: the library construction of the present invention uses a probe hybridization capture method, the library construction and hybridization capture reagents used are commercial reagents, and the probes are ...

Embodiment 1

[0087] Example 1 Characterization of patients with non-small cell lung cancer

[0088] The present invention included a total of 2300 patients with non-small cell lung cancer into the study. The characteristics of the patients are shown in Table 1. The median age at diagnosis was 63 years. There were 2066 patients with definite pathological information, 1816 (79.0%) and 250 (10.9%) patients with lung adenocarcinoma and lung squamous cell carcinoma, respectively. TMB detection was performed on 2300 patients. The median TMB of the whole population was 2.94mut / Mb (IQR, 0.74-5.88). Tumors with TMB≥10muts / Mb accounted for 12.3%. In this example, it was found that age was positively correlated with TMB (p<0.001). In addition, the TMB value of lung squamous cell carcinoma patient group (p<0.001) was higher.

[0089] Table 1. Characteristics of patients with non-small cell lung cancer

[0090]

[0091]

Embodiment 2

[0092] Example 2 The frequency of FLT3 gene mutations in Chinese NSCLC population and its correlation with immunotherapy biomarkers PD-L1 and TMB

[0093] Statistical analysis of FLT3 gene mutations in 2300 patients with non-small cell lung cancer found that 45 of the 2300 patients with non-small cell lung cancer carried FLT3 gene mutations, accounting for 1.96%. There was no significant difference in age between FLT3 mutation and wild type patients (Table 2). The TMB of FLT3 mutant patients was significantly higher than that of FLT3 wild-type patients (median TMB: 10.3vs.2.84mut / Mb, pfigure 1 ). Among the 2300 NSCLC patients, 927 tumor tissues were detected by PD-L1 immunohistochemistry, among which PD-L1 was negative (20.8% of patients with PD-L1 TPS score figure 2 ).

[0094] Table 2. Correlation between FLT3 mutations and clinicopathological features in NSCLC patients

[0095]

[0096]

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Abstract

The present invention provides the application of FLT3 gene mutation in predicting the sensitivity of non-small cell lung cancer patients to immune checkpoint inhibitor ICI therapy, and the application in predicting the degree of tumor mutation load of non-small cell lung cancer patients.

Description

technical field [0001] The invention relates to the field of clinical molecular diagnosis, in particular to the application of FLT3 gene mutation in predicting the sensitivity of ICI therapy. Background technique [0002] In recent years, tumor immunotherapy has achieved a series of breakthrough results, and has become a revolutionary treatment method in addition to surgical treatment, radiotherapy and chemotherapy, and targeted therapy, especially based on PD-1 / PD-L1, CTLA-4 and other emerging therapies. Immune checkpoint inhibitors (Immune checkpoint inhibitors, ICIs) have been widely studied in a variety of solid tumors, and have entered the first-line treatment of non-small cell lung cancer (NSCLC). Although the effect of immune checkpoint inhibitors is good, the overall objective response rate (ORR) is still only about 20%. Therefore, the development of appropriate biomarkers and accurate screening of more patients who benefit from immunotherapy are the future of tumor ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C12Q1/6886
CPCC12Q1/6886G01N33/57488G01N33/57423C12Q2600/106C12Q2600/156
Inventor 胡香静宋超邓望龙张林王晓璇陆怡李晓敏李诗濛任用
Owner NANJING SIMCERE MEDICAL LAB CO LTD
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