CN-121978332-A - Application of THY1 in diagnosis and prognosis of glioblastoma

Abstract

The invention belongs to the technical field of biological medicines, and discloses application of THY1 in diagnosis and prognosis of glioblastoma. The invention researches and identifies THY1 positive cancer related fibroblast (THY 1 + CAF) subgroup in glioblastoma for the first time, and finds that the subgroup and tumor blood vessels are highly co-located in spatial distribution, the abundance of the subgroup and the blood vessel density are obviously positively correlated, THY1 + CAF is a key cell component for promoting angiogenesis in GBM tumor microenvironment, and THY1 can be used as a GBM specific CAFs marker for the auxiliary diagnosis, prognosis evaluation (high THY1 + CAF possibly indicates worse prognosis and stronger angiogenesis phenotype) and efficacy monitoring. Meanwhile, the targeting THY1 or THY1 + CAF provides a brand-new target with potential force for developing a novel GBM therapy for resisting angiogenesis and even remodelling an immunosuppressive microenvironment.

Inventors

• LU FANGHUI
• LI DAZHEN
• Xue Jinjiang
• ZHU XINYU
• Qiao Liangjun
• XIU YUN

Assignees

• 重庆医科大学

Dates

Publication Date

20260505

Application Date

20260210

Claims (10)

1. 1. A glioblastoma diagnostic marker is characterized in that the marker is THY1 positive cancer-related fibroblast subgroup THY1 + CAF.
2. 2. A glioblastoma prognosis marker is characterized in that the marker is THY1 positive cancer-related fibroblast subgroup THY1 + CAF.
3. 3. The detection reagent for a marker according to claim 1 or 2.
4. 4. The detection reagent as set forth in claim 3, wherein the detection reagent comprises an anti-THY 1 antibody.
5. 5. The detection reagent as set forth in claim 4, wherein the detection reagent further comprises a flow cytometry reagent.
6. 6. A kit for diagnosing glioblastoma or predicting glioblastoma prognosis, characterized in that it comprises the detection reagent according to any one of claims 3 to 5.
7. 7. Use of a marker, which is a THY1 positive cancer-associated fibroblast subpopulation THY1 + CAF, in the manufacture of a product for diagnosing glioblastoma or predicting glioblastoma prognosis.
8. 8. The method of claim 7, wherein the amount of THY1 + CAF in the tumor tissue of the glioblastoma patient is significantly higher than that in normal tissue, and wherein a high THY1 + CAF indicates a worse prognosis for the patient.
9. Use of thy1 + CAF in any of the following: (1) The application of the compound serving as a target in screening anti-angiogenesis drugs in GBM tumor microenvironment; (2) The application of the glioblastoma serving as a target in screening medicaments for treating glioblastoma.
10. 10. The method of claim 9, wherein the THY1 + CAF sub-population is highly co-localized in spatial distribution with tumor vessels, and wherein the abundance is significantly positively correlated with vessel density.

Description

Application of THY1 in diagnosis and prognosis of glioblastoma Technical Field The invention belongs to the technical field of biological medicines, and relates to application of THY1 in diagnosis and prognosis of glioblastoma. Background THY1 is a glycosyl phosphatidyl inositol anchor protein (GPI-anchored protein) belonging to the immunoglobulin superfamily and having a molecular weight of about 25-37 kDa. Under normal physiological conditions, involved in fibroblast proliferation, migration and wound healing, T cell activation, apoptosis, and intercellular interactions. In solid tumors, THY1 is often used as a marker for tumor stem cells, and can mediate tumor cell-tumor cell, tumor cell-stromal cell and tumor cell-extracellular matrix interactions by binding to different ligands (e.g., integrins αvβ3, αvβ5, syndecan-4) to affect tumor cell adhesion and migration. Glioblastoma (Glioblastoma, GBM) is the primary tumor of the central nervous system with the highest malignancy and very poor prognosis. The existing treatment means (operation, radiotherapy and temozolomide amination treatment) have limited effects, and the median survival time of patients is short. Tumor Microenvironment (TME) plays a key role in the progression of GBM and in the resistance to treatment. Cancer-associated fibroblasts (CAFs) have been shown to drive tumor progression in a variety of solid tumors by promoting angiogenesis, remodeling extracellular matrix, inhibiting immunity, etc., and are important therapeutic targets. However, whether functionality CAFs exists in GBM has long been controversial, as the brain is traditionally thought to be devoid of fibroblasts. In recent years, studies have suggested the presence of CAF-like cells in GBM, but the specific subtype, molecular markers, spatial distribution characteristics and clear functions and mechanisms in GBM, particularly angiogenesis, remain unclear. This limits the development of accurate diagnostic and therapeutic methods for CAFs in GBM. There is an urgent need to identify key markers for specificity CAFs in GBM, elucidate their function, and explore their potential as new targets for therapy. Disclosure of Invention The invention aims at solving the problems and provides an application of THY1 in diagnosis and prognosis of glioblastoma. In order to achieve the purpose, the invention adopts the following technical scheme: In a first aspect the invention provides a glioblastoma diagnostic marker which is a THY1 positive cancer associated sub-population of fibroblasts THY1 + CAF. In a second aspect the invention provides a glioblastoma prognostic marker which is a sub-population of THY1 positive cancer-associated fibroblasts, THY1 + CAF. A third aspect of the present invention provides a detection reagent for the above-described marker. The detection reagent comprises an anti-THY 1 antibody. Preferably, the detection reagent further comprises a flow cytometry reagent. In a fourth aspect the invention provides a kit for diagnosing glioblastoma or predicting glioblastoma prognosis, the kit comprising the detection reagent according to any one of the preceding claims. In a fifth aspect the invention provides the use of a marker, which is a sub-population of cancers associated with fibroblast cells THY1 + CAF positive for THY1, in the manufacture of a product for diagnosing glioblastoma or predicting glioblastoma prognosis. The amount of THY1 + CAF in tumor tissue of glioblastoma patient is significantly higher than that of normal tissue, and a high THY1 + CAF indicates a worse prognosis of the patient. A sixth aspect of the invention provides the use of THY1 + CAF in any of the following: (1) The application of the compound serving as a target in screening anti-angiogenesis drugs in GBM tumor microenvironment; (2) The application of the glioblastoma serving as a target in screening medicaments for treating glioblastoma. Wherein, THY1 + CAF subgroup and tumor blood vessel are highly co-located on spatial distribution, and abundance and blood vessel density are obviously positively correlated. The beneficial effects of the invention are as follows: Through single cell transcriptome sequencing and bioinformatics analysis, and multiple immunofluorescence verification, the invention identifies THY1 positive cancer-related fibroblast (THY 1 + CAF) subgroup in glioblastoma for the first time, and finds that the subgroup and tumor blood vessels are highly co-localized in spatial distribution, and the abundance and the blood vessel density are obviously positively correlated. This suggests that THY1 + CAF is a key cellular component of pro-angiogenesis in the GBM tumor microenvironment. Therefore, THY1 can be used as a marker for GBM specificity CAFs for assisted diagnosis, prognostic assessment (high THY1 + CAF may be predictive of a worse prognosis and a stronger angiogenic phenotype) and efficacy monitoring of GBM. Meanwhile, the targeting THY1 or THY1 + CAF provides a brand-new t