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Glioma malignant progress and survival prognosis detection molecular marker, temozolomide drug resistance detection target and application

A molecular marker, temozolomide technology, applied in the field of biomedicine

Pending Publication Date: 2020-08-14
江西省肿瘤医院
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, studies have shown that glioma cells with high expression of MGMT still show resistance to temozolomide, and the clinical use of MGMT inhibitors does not improve the insensitivity of patients to temozolomide treatment.

Method used

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  • Glioma malignant progress and survival prognosis detection molecular marker, temozolomide drug resistance detection target and application
  • Glioma malignant progress and survival prognosis detection molecular marker, temozolomide drug resistance detection target and application
  • Glioma malignant progress and survival prognosis detection molecular marker, temozolomide drug resistance detection target and application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0031] Example 1 Screening of differentially expressed m6A regulators in glioma

[0032] 1. TCGA and GEPIA database analysis and screening of target genes

[0033] Methods: By analyzing the expression of m6A methylation regulators in glioma tissue and normal brain tissue in the TCGA database, the differentially expressed m6A methylation regulators were screened. And by using a large number of samples from the GEPIA database (9,736 cases of glioma and 8,587 cases of normal brain tissue), the screened differentially expressed m6A genes were verified.

[0034] Results: The analysis results showed that there were 10 genes among the 13 m6A methylation regulators: METTL3, WTAP, KIAA1429, ZC3H13, YTHDC2, YTHDF1, YTHDF2, HNRNPC, FTO and ALKBH5 expression levels were significantly different ( figure 1 A, B). Using a large number of samples in the GEPIA database to further verify the screened differential m6A regulators, it was found that HNRNPC, WTAP, YTHDF2 and YTHDF1 were significa...

Embodiment 2

[0040] Example 2 Differentially expressed m6A regulators in glioma are associated with patient survival and prognosis

[0041] 1. Expression and overall survival of m6A methylation regulators

[0042] Methods: In order to explore the correlation between m6A regulatory factors and the prognosis of glioma patients, due to the large difference in the number of glioma and normal brain tissue samples in the TCGA database, all gene expressions related to m6A methylation levels were determined. Two new glioma clusters (k=2). Through PCA principal component analysis, the transcriptional profile characteristics between clusters 1 and 2 were compared, and the survival of patients between clusters was compared.

[0043] RESULTS: Among 169 gliomas, 159 clustered in one of the clusters ( image 3 Middle A-C). The analysis found that the clinical characteristics and the expression of m6A regulators were different between the two clusters ( image 3 D), and the two clusters showed differ...

Embodiment 3

[0054] Example 3 Clinical level verification of the relationship between m6A reader HNRNPC and the occurrence and development of glioma and clinical prognosis

[0055] 1. Tissue samples to verify the association between HNRNPC expression and glioma malignancy and prognosis

[0056] Method: In order to verify whether HNRNPC plays an important role in the occurrence and development of glioma, in this embodiment of the present invention, RT-qPCR was first used to detect its expression in glioma (n=116) and normal brain tissue (n=28) The mRNA levels in the cells were further verified by Western-blot and immunohistochemical staining. Finally, the correlation analysis between the overall survival of 63 samples followed up and the expression of HNRNPC was carried out.

[0057] A method for diagnosing and detecting glioma HNRNPC disclosed in this example, takes the tumor tissue or normal brain tissue of a glioma patient, extracts total RNA according to the operation steps in the inst...

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Abstract

The invention belongs to the technical field of biomedicine, and particularly relates to a glioma malignant progress and survival prognosis detection molecular marker, a temozolomide drug resistance detection target and application. An m6A methylation reader HNRNPC which is highly expressed in glioma tissue and closely related to the tumor occurrence and development process is screened out by a bioinformatics method, further analysis finds that the expression level of the m6A methylation reader HNRNPC is closely related to the survival rate and prognosis of patients, and through clinical masstumor tissue sample verification, the m6A methylation reader HNRNPC can be used as a molecular marker and an independent survival prognosis factor for glioma malignant progress. Meanwhile, it is foundthat knockout of the HNRNPC can increase medicine sensitivity of glioma cells to temozolomide. A new diagnosis, treatment and prognosis predicting target is provided for glioma treatment, and a new molecular target can be provided for improving temozolomide drug resistance.

Description

technical field [0001] The invention belongs to the technical field of biomedicine, and in particular relates to molecular markers for detection of malignant progression and survival prognosis of glioma, targets for detection of drug resistance to temozolomide and applications thereof. Background technique [0002] Glioma is the most common primary malignant tumor of the central nervous system. Compared with other malignant tumors, the incidence rate is low, but due to the rapid proliferation and high infiltration of tumor cells, most patients will relapse even after extensive resection of normal brain tissue at the edge of the tumor. Glioblastoma multiforme is a grade IV tumor with astrocytic differentiation. It is highly aggressive, has a poor prognosis, a median survival of less than 1 year, and a very high mortality rate. Therefore, searching for molecular markers related to the occurrence and development of glioma can provide theoretical and basic experimental basis fo...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12Q1/6886
CPCC12Q1/6886C12Q2600/118C12Q2600/154C12Q2600/178
Inventor 吕巧莉陈淑慧王立冲陈俊君李敏
Owner 江西省肿瘤医院
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