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Molecular markers for glioma prognosis typing and typing method and application thereof

A molecular marker, glioma technology, applied in biochemical equipment and methods, analytical materials, biological tests, etc., can solve the problem of unknown survival and prognosis of glioma patients

Pending Publication Date: 2022-04-22
SHANGHAI NINTH PEOPLES HOSPITAL AFFILIATED TO SHANGHAI JIAO TONG UNIV SCHOOL OF MEDICINE
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0007] (1) The marker detection methods (such as sequencing, IHC, qRT-PCR, methylation sequencing) and the survival prognosis of glioma patients are unknown;
[0008] (2) The number of detected molecules in the subgroup group is large, which brings great economic burden to patients

Method used

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  • Molecular markers for glioma prognosis typing and typing method and application thereof
  • Molecular markers for glioma prognosis typing and typing method and application thereof
  • Molecular markers for glioma prognosis typing and typing method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0074] Example 1 Data set source and related verification

[0075] (1) Source

[0076] Download the malignant glioma data set and low-grade glioma data set (TCGA-GBMLGG) in the TCGA database from cBioportal, including genome, transcriptome sequencing data, methylation detection data (H450 chip) and complete clinical information, etc. , divided into small sample data set (n = 305) and large sample data set (n = 3484), for subsequent research analysis and verification.

[0077] (2) Verification

[0078] The above small sample data set and large sample data set are verified to ensure the reliability of the data set. First, confirm the prognosis of low-grade glioma samples and malignant glioma samples in the data set. The results are as follows: figure 1 As shown in A and B of A and B: the median survival time of malignant glioma in both the small sample data set and the large sample data set is significantly less than that of low-grade glioma.

[0079] Furthermore, the progno...

Embodiment 2

[0082] Different mutation types of ATRX predict the overall survival of glioma

[0083] The small sample and large sample data set in embodiment 1 are carried out the analysis of ATRX mutation type, the result finds, the mutation type of ATRX has truncation mutation (TRUNC mutation), splice body mutation (SPLICE mutation) and missense mutation (Missense mutation ), among which the highest frequency in glioma is TRUNC mutation ( image 3 B and D), the mutation often results in reduced expression of ATRX ( image 3 E).

[0084] Subsequently, the survival function Log-rank (Mantel-Cox) statistical method was used to evaluate the prognostic diagnostic value of different mutation types of ATRX in patients with glioma in a small sample data set. It was found that ATRX trunc Glioma patients mOS compared with ATRX wt The patient's mOS increased significantly (62 months vs 67.41 months, **p=0.019) ( image 3 A); further verification in a large sample data set, the results are cons...

Embodiment 3

[0090] Truncating mutations in ATRX and RNA levels of RAD51 subdivide molecular subtypes of glioma

[0091]In the same project research, the applicant of the present invention found that the RNA expression level of RAD51 can significantly predict the prognosis and survival time of glioma patients after conventional treatment. The combined prognostic diagnostic value of RAD51 RNA levels was analyzed and evaluated.

[0092] The result is as Figure 5 Shown in A and B: Combining truncating mutations in ATRX and RNA expression levels of RAD51, we subdivided glioma patients into four subgroups, which exhibited ATRX wild-type and RAD51 RNA high expression (>75% quantile number, RAD51 RNA_high ) patients with glioma had the worst survival period (n=305 discovery population, the overall survival time was only 19.9 months, **p=0.0012; n=3484 verification population, the overall survival time was only 17.6 months, *** *p<0.0001), which coincides with the average survival time of mali...

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Abstract

The invention discloses a group of molecular markers for glioma prognosis typing and a typing method and application thereof, and belongs to the field of disease prognosis. The molecular marker comprises ATRX and RAD51, a specific mutation type based on ATRX is combined with RAD51 mRNA or DNA methylation level detection, the lifetime of a glioma patient can be predicted, the patient is divided into four subtypes more carefully according to a detection result, and a potential drug target is provided for effective treatment of glioma. The invention also provides application of a specific detection index method of ATRX and RAD51 in glioma molecular subtypes through research, and provides more sufficient data support for application of the marker. The marker has the advantages of simplicity and convenience in operation, low cost, good effect and the like on prognosis typing and evaluation of glioma, and is easy for clinical popularization of medical institutions.

Description

technical field [0001] The invention belongs to the field of disease prognosis, and in particular relates to a group of molecular markers for prognostic typing of glioma and a typing method and application thereof. Background technique [0002] Glioma is the most common primary brain tumor originating from glial cells in the brain and spinal cord, accounting for about 77% of tumors originating in the central nervous system. According to the glial cell morphology, it is divided into oligodendroglioma, ependymal neurocytoma and astrocytoma. The World Health Organization (WHO) further divides astrocytoma into four grades (WHO I-IV) according to histomorphology, grade I is fibrous astrocytoma (Pilocytic Astrocytoma, PA), grade II is diffuse Astrocytoma (Diffuse Astrocytoma, DA), grade III is anaplastic astrocytoma (Anaplastic Astrocytoma, AA), grade IV is malignant glioma (Glioblastoma, GBM). According to the degree of malignancy, WHO grade I / II is collectively referred to as ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12Q1/6886C12N15/11G01N33/68G01N33/574
CPCC12Q1/6886G01N33/68G01N33/57407G01N33/57484C12Q2600/118C12Q2600/112C12Q2600/158C12Q2600/154G01N2800/54G01N2800/50G01N2800/52
Inventor 杨庆源季天海韩晨杰朱金潮龙满美郑海燕
Owner SHANGHAI NINTH PEOPLES HOSPITAL AFFILIATED TO SHANGHAI JIAO TONG UNIV SCHOOL OF MEDICINE
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