Gene marker for glioma prognosis and application thereof

A glioma and marker technology, applied in the field of molecular biology, can solve problems such as unclear and unseen

Pending Publication Date: 2022-05-13
THE FIRST AFFILIATED HOSPITAL OF ARMY MEDICAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] Inducing tumor ferroptosis is a very promising anti-cancer approach, but how to induce ferroptosis in glioma, whether ferroptosis inducers affect the invasive growth of glioblastoma cells, and which ferroptosis-related regulators Involvement in temozolomide resistance and other issues is unclear
Therefore, there has not been seen in the prior art the use of ferritin light chain (FTL) and ferritin heavy chain 1 (FTH1) as prognostic indicators, especially as prognostic indicators of glioma, or as anti-inflammatory agents of related chemotherapy drugs. Applied reports on performance indicators, etc.

Method used

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  • Gene marker for glioma prognosis and application thereof
  • Gene marker for glioma prognosis and application thereof
  • Gene marker for glioma prognosis and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0042] Example 1 Correlation between FTH1 and FTL and TMZ drug resistance

[0043]Since the induction of ferroptosis enhanced the inhibitory effect of TMZ on GBM cells, first, based on the analysis of several key regulators of ferroptosis, including GPX4, SLC7A11, FTH1, FTL, TF, TFRC, TFR2, NQO1 and ATL1. Then through the analysis of TCGA_GBMLGG database, it was found that FTH1 and FTL had the greatest correlation with GPX4. GSEA of the Hallmark gene set showed that FTH1 High to FTH1 Low 、FTL High to FTL Low , GPX4 High to GPX4 Low Most of the enriched gene sets overlapped ( Figure 1A ). Notably, these three groups of cells were continuously enriched in the gene set of the oxidative stress pathway, which has been shown to be an important regulator of ferroptosis in cancer cells. The high expression of GPX4, FTH1 (SEQ ID NO:4) and FTL (SEQ ID NO:2) can enrich the genes related to epithelial-mesenchymal transition, and the enrichment scores of FTH1 and FTL are higher tha...

Embodiment 2

[0044] Example 2 Correlation between FTH1 and FTL and GBM progression and poor survival

[0045] Through the immunohistochemical analysis of 171 glioma samples (cohort-171), it was found that the expression of FTH1 and FTL increased with the increase of glioblastoma grade I to grade IV ( Figure 2A ). Kaplan-Meier survival analysis of tissue microarrays showed that, with FTH1 Low or FTL Low patients compared with FTH1 High or FTL High The prognosis of patients was significantly worse ( Figure 2B ). Cases with simultaneous high expression of FTH1 and FTL (FTH1 High / FTL High ) was significantly shorter than FTH1 and other expression states of FTL such as FTH1 High / FTL Low , FTH1 Low / FTL High or FTH1 Low / FTL Low ( Figure 2C ). Simply put, FTH1 High / FTL High Glioma patients have significantly better prognosis than other non-FTH1 High / FTL High Glioma patients are poor ( Figure 2D ). Data from TCGA_GBMLGG also consistently showed that high expression of...

Embodiment 3

[0046] Example 3 Verification experiment by gene expression and western blotting

[0047] FTH1 and FTL are biological markers. 1. The expression of FTH1 and FTL can be judged by obtaining the tumor area tissue of the patient through pathology, and performing gene level detection or protein level detection.

[0048] 1. Detection at the genetic level:

[0049] The DNA content of FTH1 and FTL can be detected by next-generation sequencing of the patient's tumor tissue, or the mRNA level of FTH1 and FTL can be detected by polymerase chain reaction PCR. The FTL-mRNA sequence is SEQ ID NO: 1, and the FTH1-mRNA sequence is SEQ ID NO: 3.

[0050] If the expression levels of FTH1 and FTL genes are higher than normal, it indicates that the prognosis of the patient is poor. Such as Figure 2B -E can prove this point, such as Figure 2A Shown: The glioma patients with high expression of FTH1 and FTL have a higher grade, indicating a higher degree of malignancy. Figure 2B -E indicates...

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Abstract

The invention provides a biomarker for detecting glioma prognosis or temozolomide drug resistance. The biomarker comprises a first marker for displaying the expression level of a ferritin light chain (FTL) and a second marker for displaying the expression level of a ferritin heavy chain 1 (FTH1). The invention also provides an application of the gene in preparation of a diagnostic reagent. The invention provides a very clear indication index for glioma prognosis, and successfully provides a guiding reference for clinical prognosis prediction and treatment modes of patients.

Description

technical field [0001] The invention relates to the technical field of molecular biology, in particular to a gene marker for glioma prognosis and its application. Background technique [0002] Ferroptosis is a new mode of cell death, which is an iron ion-dependent non-apoptotic cell death mode. In 2003, it was first discovered by Dolma et al. when studying the mechanism of the small molecule drug Erastin on tumor cells with mutations in the Ras gene. Until 2012, Dixon reported that this mode of cell death relies on iron ions and reactive oxygen species to induce lipid peroxidation, which leads to regulation. The cells die and are named ferroptosis or ferroptosis. This mode of cell death is obviously different from other forms of apoptosis, necrosis, and autophagy at the morphological, biological, and genetic levels, and cannot be prevented by inhibitors of apoptosis or necrosis, but ferroptosis can be prevented by small molecule iron chelators. Deferoxamine (ferrostatin-1)...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12Q1/6886G01N33/574
CPCC12Q1/6886G01N33/57407G01N33/57484C12Q2600/158C12Q2600/118C12Q2600/106G01N2333/47
Inventor 杨飞城王岩覃艳
Owner THE FIRST AFFILIATED HOSPITAL OF ARMY MEDICAL UNIV
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