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Application of pcdh11x mutation in predicting sensitivity to immune checkpoint inhibitor therapy in patients with non-small cell lung cancer

1. PCDH11X, non-small cell lung cancer technology, applied in the direction of microbial determination/inspection, measuring devices, biochemical equipment and methods, etc., can solve the problems of lack of detection methods

Active Publication Date: 2022-03-25
SIMCERE DIAGNOSTICS CO LTD +2
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the DDR pathway involves many genes, and there is currently a lack of easy detection methods

Method used

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  • Application of pcdh11x mutation in predicting sensitivity to immune checkpoint inhibitor therapy in patients with non-small cell lung cancer
  • Application of pcdh11x mutation in predicting sensitivity to immune checkpoint inhibitor therapy in patients with non-small cell lung cancer
  • Application of pcdh11x 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 1

[0110] Example 1 Analysis of the relationship between PCDH11X gene mutation and immunotherapy efficacy in clinical cohorts

[0111]In the Hellmann cohort, there were 15 patients (20%) with PCDH11X mutations, and the median PFS after immunotherapy was longer in patients with PCDH11X mutations than in patients with wild-type PCDH11X (median OS: 13.53 vs. 4.43 months; log-rank test , p=0.02) ( figure 1 ), suggesting that PCDH11X can be used as a predictor of immunotherapy efficacy. Further, the present invention is verified in the Miao cohort. In the Miao cohort, there are 7 cases (12.5%) of patients with PCDH11X mutation, and the median OS of patients with PCDH11X mutation after receiving immunotherapy is longer than that of patients with wild type PCDH11X (median OS : 14.7vs.8.09 months; log-rank test, p=0.046)( figure 2 ).

[0112] Further, the present invention analyzes the relationship between PCDH11X gene mutation and ORR. In order to obtain more statistically signific...

Embodiment 2

[0115] Example 2 Correlation between PCDH11X gene mutation and immunotherapy biomarker PD-L1 gene expression level

[0116] Detection of tumor PD-L1 expression based on immunohistochemical staining is currently the most widely used biomarker for immunotherapy. The present invention explores the correlation between PCDH11X gene mutation and PD-L1 gene expression level. In the TCGA-LUAD cohort, the expression of PD-L1 gene in tumor tissues of patients with PCDH11X mutation was significantly higher than that of patients with wild type PCDH11X (log2(fold change)=0.7, p=0.032)( Figure 4 ); in the TCGA-LUSC cohort, PD-L1 gene expression levels were not significantly different between PCDH11X mutant and wild-type patients ( Figure 5 ).

[0117] This example analyzes the relationship between PCDH11X mutation and PD-L1 gene expression level in two cohorts, indicating that PCDH11X mutation can be used as an indication of high PD-L1 expression at least in lung adenocarcinoma, and fur...

Embodiment 3

[0118] Example 3 Correlation between PCDH11X gene mutation and immunotherapy biomarker TMB

[0119] TMB is the most widely used marker for predicting curative effect of immunotherapy. The present invention explores the relationship between PCDH11X gene mutation and TMB. In the Hellmann&Miao dataset, the TMB of PCDH11X mutation patients was significantly higher than that of PCDH11X wild-type patients (median TMB: 40.11vs.11.80MUT / Mb, p Image 6 ). Likewise, in the TCGA-LUAD and TCGA-LUSC cohorts, patients with PCDH11X mutations had significantly higher TMB than PCDH11X wild-type patients ( Figure 7 , Figure 8 ).

[0120] Therefore, this example verifies the relationship between PCDH11X mutation and TMB in multiple cohorts, indicating that PCDH11X mutation can be used as an indication of high TMB, and further suggests that PCDH11X mutation can predict the efficacy of immunotherapy for non-small cell lung cancer.

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Abstract

The present invention relates to the role of PCDH11X mutations in predicting the sensitivity of non-small cell lung cancer patients to immune checkpoint inhibitor therapy, as well as in predicting tumor mutation load, DNA mismatch repair pathway gene mutations, and the degree of immune cell infiltration in tumors in patients with non-small cell lung cancer application.

Description

technical field [0001] The invention relates to the field of molecular diagnosis, in particular to the application of PCDH11X mutation in predicting the sensitivity of non-small cell lung cancer patients to immune checkpoint inhibitor therapy. Background technique [0002] In recent years, treatments based on PD-1 / PD-L1, CTLA-4 and other emerging immune checkpoint inhibitors (Immune checkpoint inhibitors, ICIs) have been widely studied in various solid tumors, and have entered non-small cell lung cancer. (NSCLC) first-line treatment. Although the effect of immune checkpoint inhibitors is good, the overall objective response rate (ORR) is still only about 20%. Therefore, the development of suitable biomarkers to accurately screen more patients who benefit from immunotherapy is an urgent problem to be solved in the future development of tumor immunotherapy The key issue. [0003] Detection of tumor PD-L1 expression based on immunohistochemical staining is currently the most ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C12Q1/6886G01N33/574
CPCC12Q1/6886G01N33/57423G01N33/57488C12Q2600/106C12Q2600/156
Inventor 刘满姣郭昊颜林林葛明晖薛方方李诗濛任用
Owner SIMCERE DIAGNOSTICS CO LTD
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