Genetic marker for risk assessment on AML (acute myelogenous leukemia) and application of genetic marker

A technology for acute myeloid and leukemia, applied in the field of diagnosis, which can solve the problem that predictors have no prognostic effect, etc.

Inactive Publication Date: 2019-03-01
RUIJIN HOSPITAL AFFILIATED TO SHANGHAI JIAO TONG UNIV SCHOOL OF MEDICINE
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

Fourth, there are often co-occurrence or mutual exclusion between different gene mutations, so many existing predictors have no independent prognostic effect

Method used

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  • Genetic marker for risk assessment on AML (acute myelogenous leukemia) and application of genetic marker
  • Genetic marker for risk assessment on AML (acute myelogenous leukemia) and application of genetic marker
  • Genetic marker for risk assessment on AML (acute myelogenous leukemia) and application of genetic marker

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0206] Example 1, CEBPe expression is significantly high in known AML patients with better prognosis

[0207] The present inventors collected AML patient expression profile data including prognostic classification information from public databases. Among them, there are 184 samples in TCGA, 186 samples in GSE14468, and 260 samples in GSE1159. The inventors found that in these three independent data sets, CEBPe was significantly overexpressed in samples known to have a better prognosis. The P values ​​of differential expression of CEBPe in samples with good prognosis and poor prognosis were 5.021e-05, 2.813e-11, and 1.217e-6, respectively (see figure 1 A).

[0208] In the TCGA data, most of the samples with the highest expression of CEBPe had a better prognosis (see figure 1 B).

Embodiment 2

[0209] Example 2, CEBPe expression has a predictive effect on overall survival and disease-free survival

[0210] In three independent data sets of TCGA, GSE1159, and GSE10358, all samples in each data set were sorted according to the expression value of CEBPe from high to low. The samples with the top quartile of CEBPe expression values ​​were classified as CEBPe high-expressing samples, and the remaining three-quarters of samples were classified as CEBPe-low expressing samples.

[0211] The results showed that the survival time of CEBPe high expression group was significantly longer than other samples. In TCGA, GSE1159, and GSE10358, the overall survival rates of high / low expression samples were 38% / 17%, 41% / 23%, 59% / 35%; the disease-free survival rates were 47% / 23%, 40% % / 21%, 62% / 37%. CEBPe's ability to predict overall survival and disease-free survival in three sets of independent data sets was significant (see image 3 ).

Embodiment 3

[0212] Example 3, CEBPe expression can predict the recurrence of AML

[0213] The present inventors used two sets of data sets, TCGA and GSE1159, which contain patient recurrence information, to evaluate the predictive ability of CEBPe expression for recurrence in AML patients. By using the K-nearest neighbor classification method, all samples were divided into CEBPe high expression group and low expression group, and then the recurrence of samples in the two groups was compared.

[0214] The results showed that CEBPe expression had a significant predictive effect on the recurrence rate of patients (see Figure 4 ). The recurrence rate of samples with high expression of CEBPe was significantly lower than that of samples with low expression.

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Abstract

The invention relates to a genetic marker for risk assessment on AML (acute myelogenous leukemia) and application of the genetic marker. The inventor generally analyzes a key gene causing occurrence of AML and development of the disease and identifying CEBPe as a key gene causing survival and recurrence of AML by integrating clinical experimental data and public data resources and utilizing various bioinformatics analysis methods, so that a diagnosis method and a diagnosis kit taking the CEBPe as a target spot are provided. The bioinformatics analysis thinking and methods and the related diagnosis kit are especially suitable for analyzing and predicting the survival time and the recurrence sitation of AML clinical patients. Additionally, the gene diagnosis kit taking the CEBPe as the target spot can also be used for subdividing non-aged AML patients and AML patients having middle and low risks, such as an oncogenic non-mutation sample and the like, and guiding whether allogeneic bone marrow transplantation is conducted.

Description

technical field [0001] The invention belongs to the technical field of diagnosis, and more specifically, the invention relates to acute myeloid leukemia risk assessment gene markers and applications thereof. Background technique [0002] Acute myeloid leukemia (AML) is a malignant tumor caused by hematopoietic stem cell differentiation disorder, apoptosis escape and uncontrolled proliferation, which seriously threatens human life and health. AML has the characteristics of high heterogeneity, poor prognosis and easy recurrence. With the acceleration of the aging process of the global population, the incidence of AML has increased significantly. Therefore, digging out new targets for AML diagnosis, treatment and prognosis in an all-round way has become an urgent task for current researchers. [0003] Currently, the treatment methods for AML mainly include chemotherapy and allogeneic bone marrow transplantation. Through the detection of chromatin structure variation and gene...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12Q1/6886G01N33/574
CPCC12Q1/6886C12Q2600/118C12Q2600/158G01N33/57426G01N2333/47
Inventor 张济李科宁王海伟
Owner RUIJIN HOSPITAL AFFILIATED TO SHANGHAI JIAO TONG UNIV SCHOOL OF MEDICINE
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