Application of PTPRD gene mutation in predicting immunotherapy sensitivity of TP53 mutant lung cancer patient

A mutation-type, patient-oriented technology, applied in measuring devices, microbial measurement/inspection, instruments, etc., can solve problems such as tumor specificity, tumor heterogeneity, and no effective treatment methods, achieve reliable results, and improve detection efficiency effect

Inactive Publication Date: 2021-10-29
NANFANG HOSPITAL OF SOUTHERN MEDICAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, there are still some problems with these predictors: such as predictive efficiency, tumor heterogeneity, tumor specificity, etc.
These results suggest that TP53 mutant tumors may be a type of tumor that is relatively sensitive to ICIs treatment. However, there is still no effective treatment for TP53 mutant NSCLC.

Method used

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  • Application of PTPRD gene mutation in predicting immunotherapy sensitivity of TP53 mutant lung cancer patient
  • Application of PTPRD gene mutation in predicting immunotherapy sensitivity of TP53 mutant lung cancer patient
  • Application of PTPRD gene mutation in predicting immunotherapy sensitivity of TP53 mutant lung cancer patient

Examples

Experimental program
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Effect test

Embodiment 1

[0026] Application of PTPRD gene mutation as a biomarker in predicting sensitivity to immune checkpoint inhibitor therapy in patients with TP53-mutant lung cancer.

[0027] In this example, the DNA of 348 NSCLC patients receiving immunotherapy in MSK Cancer Center was sequenced, and the results were analyzed as follows figure 1 shown. Among them, the mutation rate of TP53 was 62.1% (216 / 348). figure 1 These 216 TP53 mutant patients are KRAS (25.9%), KEAP1 (19.4%), PTPRD (15.7% ), EGFR (14.8%), STK11 (13.4%), PTPRT (13.0%) and SMARCA4 (9.3%).

[0028] Multivariate Cox regression analysis was performed on patients with TP53 mutations to screen independent prognostic genes that were significantly effective in immunotherapy for TP53-mutant lung cancer. STK11, PTPRT and SMARCA4), using the backward:conditional method. The final results showed that only PTPRD mutation can be used as an independent predictor for TP53 mutant NSCLC to receive immunotherapy (HR=1.848; P=0.025). The ...

Embodiment 2

[0038] Effect of PTPRD gene mutation on immune microenvironment in patients with TP53 mutant NSCLC

[0039] In order to elucidate the internal factors of the remarkable efficacy of immunotherapy in patients with TP53 / PTPRD double mutations, the present invention analyzes the mutation status of TP53 and PTPRD genes in the TCGA (The CancerGenome Atlas) database of lung cancer through the method of gene set enrichment analysis (GSEA) The effect on the signal pathway of gene enrichment, the results are as follows Figure 4 shown. pass Figure 4 A, 4B shows that TP53 突变 / PTPRD 突变 Double mutant group compared to TP53 突变 / PTPRD 野生 group significantly up-regulated interferon gene stimulator (cGAS-STING) signaling pathway and IFN-β signaling pathway. also, Figure 4 C, 4D can be seen, lung cancer TCGA database analysis shows that TP53 突变 / PTPRD 突变 Compared with other subgroups, the RNA expression of STING1 and its downstream key gene IRF3 was significantly higher in the subgroup...

Embodiment 3

[0046] Embodiment 3PTPRD gene mutation site analysis

[0047] The mutation site of PTPRD gene was analyzed, and the results were as follows: Figure 7 shown. It was found that the variants of PTPRD gene were mainly missense mutations, followed by truncation mutations and whole code mutations. Gene mutation sites are relatively scattered, and there is no obvious hotspot mutation area.

[0048] In conclusion, PTPRD gene mutation can be used as a predictor of sensitivity to immune checkpoint inhibitor therapy in patients with TP53 mutant lung cancer.

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Abstract

The invention relates to an application of gene mutation in predicting immunotherapy sensitivity of a lung cancer patient, in particular to application of PTPRD gene mutation in predicting immunotherapy sensitivity of a TP53 mutant lung cancer patient and application of a PTPRD gene mutation detection product in preparing a product for predicting sensitivity of the TP53 mutant lung cancer patient to immune checkpoint inhibitor therapy. The existence of PTPRD gene mutation is an indication that the TP53 mutant lung cancer patient is sensitive to immune checkpoint inhibitor therapy. According to the application, the PTRPD mutant gene is screened as a population biomarker for predicting ICI sensitivity in the TP53 mutant lung cancer patient; and through PTRPD mutation, the tumor lymphocyte infiltration and PD-L1 expression level of the TP53 mutant lung cancer patient can be predicted, then ICI sensitive populations are predicted, and more immunotherapy benefited populations are accurately screened.

Description

technical field [0001] The present invention relates to the application of gene mutation in predicting the immunotherapy sensitivity of lung cancer patients, in particular to the application of PTPRD gene mutation in predicting the immunotherapy sensitivity of TP53 mutant lung cancer patients. Background technique [0002] Lung cancer is the most common malignant tumor in humans. The occurrence and development of lung cancer are closely related to driver gene mutations, and molecular targeted therapy derived from driver gene mutations has made a major breakthrough in the treatment of lung cancer. However, the emergence of drug resistance limits the continuous benefit of patients. In recent years, with the rise of immunotherapy, more and more studies have found that there is an intrinsic relationship between driver gene variation and immunotherapy resistance in lung cancer. For example, the efficacy of immunotherapy in patients with EGFR-mutated NSCLC decreases, while TP53 / K...

Claims

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Application Information

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IPC IPC(8): C12Q1/6886G01N33/574
CPCC12Q1/6886G01N33/57484G01N33/57423C12Q2600/106C12Q2600/156
Inventor 董忠谊吴德华白雪蔡晓庭谭家乐
Owner NANFANG HOSPITAL OF SOUTHERN MEDICAL UNIV
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