Marker of mesenchymal subtype glioblastoma and application thereof

A glioblastoma and marker technology, applied in the field of mesenchymal subtype glioblastoma markers, can solve the problems of unclear and change the progress and outcome of glioma

Pending Publication Date: 2022-05-10
THE FIRST HOSPITAL OF CHINA MEDICIAL UNIV
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, so far, whether chemokines can change the progression and outcome of glioma by affecting the transformation of glioma phenotype and the structure of the immune microenvironment is still unclear.

Method used

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  • Marker of mesenchymal subtype glioblastoma and application thereof
  • Marker of mesenchymal subtype glioblastoma and application thereof
  • Marker of mesenchymal subtype glioblastoma and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0079] Example 1 Tumor-derived chemokines positively regulate the mesenchymal characteristics of GBM.

[0080] To explore the microenvironmental characteristics of different GBM molecular subtypes, we analyzed the transcriptomic data of GBM patients in the CGGA and TCGA databases. Cluster analysis based on immune cell gene set scores showed that the mesenchymal subtype GBM was mainly enriched in Cluster I (chi-square test, pfigure 1 A). By comparing the CIBERSORT immune cell enrichment scores between mesenchymal subtypes and other non-mesenchymal subtypes of GBM, we found that the most significantly enriched immune cell species in mesenchymal subtypes of GBM were M0 or M2 type TAMs ( figure 1 B). Moreover, the macrophage gene set GSVA score was correlated with judging whether the GBM tissue was a mesenchymal subtype ( figure 1 C), the ssGSEA score of the mesenchymal signature gene set ( figure 1 D; Table 1), the expression levels of mesenchymal phenotype-related transcript...

Embodiment 2

[0090] Example 2 Chemokines enhance the mesenchymal characteristics of GBM cells through autocrine pathways

[0091] In order to elucidate the role of chemokines in regulating the mesenchymal characteristics of GBM cells, we used GSCs cells stimulated by TNF-α, a proven enhancer of mesenchymal characteristics of GBM cells, as a positive control, and the GSCs cells were subjected to 48h chemotaxis. After stimulation with recombinant proteins, they were subjected to RNA sequencing. The results showed that GSCs treated with chemokine recombinant protein all had higher Verhaak mesenchymal clustering scores and other mesenchymal characteristic gene set GSVA scores ( Figure 4 A). To further clarify the effect of chemokines on the mesenchymal characteristics of GBM cells, we overexpressed chemokines in GSC1 and GSC28 cells and knocked down chemokines in GSC1 and GSC40 cells ( image 3 F). The results found that similar to the cells treated with TNF-α recombinant protein, overexpr...

Embodiment 3

[0092] Example 3. CMKLR1 plays a key role in GBM cell transduction chemokine signal process

[0093] Previous studies have found that the main receptor that binds to chemokines on the cell surface is CMKLR1. Similar to the RARRES2 expression pattern, CMKLR1 is highly expressed in the mesenchymal subtype GBM ( Figure 5 A). Although CMKLR1 has prognostic value only in the Rembrandt GBM database ( Figure 5 B), but it is the basis for the ability of RARRES2 to exert the prognostic assessment ability of GBM patients. We found that RARRES2 could exert its prognostic value only in the population of GBM patients with high expression of CMKLR1 but not in the population of GBM patients with low expression of CMKLR1 ( Figure 5 C). In addition, patients with high expression of CMKLR1 and RARRES2 had a significantly higher chance of suffering from mesenchymal subtype GBM (Table 4), suggesting a close correlation between chemokine / CMKLR1 expression levels and mesenchymal subtype GBM....

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Abstract

The invention belongs to the technical field of medical biology, and particularly relates to a mesenchymal subtype glioblastoma marker and application thereof. According to the invention, the positive correlation between the chemokine / CMKLR1 axis and the cell migration / invasion ability of the tumor cells and the expression level of the mesenchymal marker is proposed for the first time, the mesenchymal subtype GBM can be subjected to auxiliary diagnosis by detecting the expression level of the chemokine / CMKLR1 axis, and a reference basis is provided for clinical doctors to diagnose central nervous system tumors. When the CMKLR1 is knocked down and an antibody is neutralized by using a CMKLR1 blocking agent alpha-NETA or a chemotactic element, an inhibition effect can be generated on the migration / invasion ability of mesenchymal subtype GBM cells and the expression level of a mesenchymal marker. The chemokine / CMKLR1 axis can be used as a potential target spot for GBM treatment, and has important significance on tumor treatment.

Description

technical field [0001] The invention belongs to the technical field of medicine and biology, and in particular relates to a marker of mesenchymal subtype glioblastoma and its application. Background technique [0002] Glioblastoma (GBM) is the most common and aggressive primary brain tumor. Although the combined treatment of radiotherapy and chemotherapy has improved and enhanced the therapeutic effect of glioblastoma to a certain extent, the median survival time of GBM patients is still less than 15 months, and the survival rate is less than 10%. Therefore, more effective treatments are urgently needed. treatment strategy. The molecular typing of GBM is very important for elucidating the molecular mechanism of the occurrence and development of glioma, establishing a personalized and precise diagnosis and treatment plan, and developing effective therapeutic drugs. The study found that no matter the mesenchymal subtype GBM clustered by the Verhaak molecular typing system or...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12Q1/6886G01N33/574
CPCC12Q1/6886G01N33/57407G01N33/57484C12Q2600/118C12Q2600/158
Inventor 吴安华吴建奇沈帅刘天奇程文
Owner THE FIRST HOSPITAL OF CHINA MEDICIAL UNIV
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