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Application of BGN gene in predicting treatment effect of immune checkpoint inhibitor of colon cancer patient

A technology for immune checkpoints and therapeutic effects, applied in measurement devices, instruments, disease diagnosis, etc., can solve problems such as lack of molecular markers

Pending Publication Date: 2022-03-15
中国人民解放军海军军医大学第一附属医院
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Unfortunately, in current clinical practice, there is a lack of a molecular marker with good predictive performance to predict the immune status of colon cancer patients and the response rate of immune checkpoint inhibitor therapy

Method used

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  • Application of BGN gene in predicting treatment effect of immune checkpoint inhibitor of colon cancer patient
  • Application of BGN gene in predicting treatment effect of immune checkpoint inhibitor of colon cancer patient
  • Application of BGN gene in predicting treatment effect of immune checkpoint inhibitor of colon cancer patient

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0027] Example 1, Screening of Differential Genes

[0028] In this example, three GEO data sets (GSE4107, GSE110224, GSE4183), including 44 colon cancer tissues and 35 normal tissues, were analyzed to determine differentially expressed genes. According to the set criteria, 1039, 396 and 256 differentially expressed genes were obtained, respectively. Such as figure 1 As shown in A, 14 differentially expressed genes with overlapping expression were screened out. Subsequently, the protein-protein interaction network (PPI network) was constructed by the STRING tool, and the results are as follows figure 1 As shown in B, it can be seen that ABCG2, CXCL8, CXCL12, BGN, SULF1, THBS2 and FAP interact. Then upload the PPI network to the Cytoscape software. According to the ratio of matrix-immune components in the TME of each sample generated by the CytoHubba module in the Cytoscape software, it is known from the grade scores calculated by the ESTIMATE package in R. ABCG2, CXCL8, CXCL...

Embodiment 2

[0029] Example 2. Correlation between BGN expression level and immune score, matrix score and ESTIMATE score in tumor immune microenvironment

[0030] In this example, the correlation analysis between the expression of BGN and the immune score, matrix score and ESTIMATE score of colon cancer is carried out. The specific method is as follows: through the ESTIMATE package in R software, the tumor immune microenvironment of each sample of TCGA colon cancer is calculated and analyzed The ratio of matrix-immune components in the medium. A higher immune or stromal score represents a larger proportion of immune or stromal components in the tumor immune microenvironment, while the ESTIMATE score represents their combined proportion. The result is as figure 2 Shown: Pearson correlation analysis found that in colon cancer, the expression of BGN was positively correlated with immune score, matrix score and ESTIMATE score, that is, the higher the expression of BGN, the higher the immune...

Embodiment 3

[0031] Example 3, the role of BGN in regulating the polarization of macrophages in colon cancer

[0032] In order to further study the relationship between BGN and immune cell subtypes in colon cancer tissues, this example analyzed the proportion of tumor-infiltrating immune cells (TIICs) in the TCGA database using the quantIseq method. Among these subtypes of TIICs, macrophages (M1+M2) accounted for about 38% of colon cancer tissues (M1 about 27%, M2 about 11%), neutrophils about 32% of colon cancer tissues, CD4+ T cells account for 10% of colon cancer tissues, and NK cells account for 7% of colon cancer tissues. Subsequently, we explored the relationship between the expression level of BGN and the infiltration of 10 immune cells in colon cancer ( image 3), the results showed that the expression of BGN had the most obvious relationship with the macrophage M2 population (Macrophage M2) and regulatory T cell (Regulatory T cell) population. Next, we verified the association o...

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Abstract

The invention discloses an application of a BGN gene in predicting the therapeutic effect of an immune checkpoint inhibitor of a colon cancer patient, and the BGN gene is used as an effective biomarker for predicting the therapeutic effect of the immune checkpoint inhibitor of the colon cancer patient, so that the patient who is most likely to benefit from the immune checkpoint inhibitor therapy can be identified. The invention provides a reliable and convenient immune checkpoint inhibitor treatment response rate prediction index, and has a positive effect on clinical medication guidance and precise treatment of colon cancer patients.

Description

technical field [0001] The invention relates to the technical field of predicting the therapeutic effect of immune checkpoint inhibitors, in particular to the use of a BGN gene in predicting the therapeutic effect of immune checkpoint inhibitors in patients with colon cancer. Background technique [0002] The 2020 global cancer statistics show that colorectal cancer (CRC) ranks third among the most common malignancies and second among cancer-related deaths. CRC accounts for 1.9 million new cases and 935,000 deaths each year, accounting for 9.8% of the total cancer incidence and 9.2% of the mortality rate (Arnold, Sierra et al., 2017; Sung, Ferlay et al., 2021). Although the application of colonoscopy screening and imaging techniques such as CT three-dimensional reconstruction or PET-CT has improved the diagnosis rate of CRC in recent years, about 25% of patients will progress to advanced tumors (Ganesh, Stadler et al., 2019 ), these patients have limited benefit from conven...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): G01N33/577G01N33/574
CPCG01N33/577G01N33/57419G01N33/57484G01N2800/52
Inventor 柏愚贺子轩彭立嗣方雪康乐王智杰李兆申袁捷张德宇
Owner 中国人民解放军海军军医大学第一附属医院