CN112760372A - Myocardial infarction differential expression gene and application thereof - Google Patents

Myocardial infarction differential expression gene and application thereof Download PDF

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Publication number
CN112760372A
CN112760372A CN202110307455.8A CN202110307455A CN112760372A CN 112760372 A CN112760372 A CN 112760372A CN 202110307455 A CN202110307455 A CN 202110307455A CN 112760372 A CN112760372 A CN 112760372A
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China
Prior art keywords
tex30
znf420
gene
myocardial infarction
agent
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CN202110307455.8A
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Chinese (zh)
Inventor
赵强
李正美
赵洋
康玲
江科
李元民
姜广运
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Shandong First Medical University and Shandong Academy of Medical Sciences
Second Affiliated Hospital of Shandong First Medical University
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Second Affiliated Hospital of Shandong First Medical University
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    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6876—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
    • C12Q1/6883—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
    • G01N33/6893—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids related to diseases not provided for elsewhere
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q2600/00—Oligonucleotides characterized by their use
    • C12Q2600/158—Expression markers
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
    • G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
    • G01N2333/46—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans from vertebrates
    • G01N2333/47—Assays involving proteins of known structure or function as defined in the subgroups
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2800/00—Detection or diagnosis of diseases
    • G01N2800/32—Cardiovascular disorders
    • G01N2800/324—Coronary artery diseases, e.g. angina pectoris, myocardial infarction

Abstract

The invention discloses a myocardial infarction differential expression gene and application thereof, wherein the biomarker comprises TEX30 and/or ZNF 420. The invention discloses that TEX30 and ZNF420 show significant difference in myocardial infarction patients compared with normal people, and an ROC curve shows that the patient has a higher AUC value, which indicates that TEX30 and/or ZNF420 can be applied to myocardial infarction diagnosis. The invention provides a product for diagnosing myocardial infarction. The invention also provides a pharmaceutical composition for treating myocardial infarction.

Description

Myocardial infarction differential expression gene and application thereof
Technical Field
The invention relates to the field of biomedicine, in particular to a myocardial infarction differential expression gene and application thereof.
Background
According to the latest statistics of epidemiology, cardiovascular diseases are the first causes of death of residents in China, the number of deaths accounts for more than 40% of the total number of deaths of the residents, and the incidence of myocardial infarction is rapidly increased in recent years and becomes one of the diseases which seriously affect the health of the people. The myocardium is gradually necrosed after myocardial infarction, and a series of clinical events such as heart failure, myocardial rupture or arrhythmia are further formed. In order to prevent myocardial necrosis, early treatment of myocardial ischemia, such as fibrinolysis, coronary artery bypass graft, PCU, etc., can significantly improve prognosis. Despite the continuous development of research on cardiovascular diseases and the significant improvements in the diagnosis and treatment of myocardial infarction over the past decade, myocardial infarction remains a highly fatal disease.
Molecular markers are biological parameters that can be measured quantitatively as indices of health and physiological assessment. It provides risk and diagnostic information for the disease. Myocardial infarction diagnosis currently relies on the elevation or decline of cardiac troponin (at least one of which exceeds the 99 th percentile of the upper reference value) and incorporates one of the following symptoms: (1) symptoms of ischemia; (2) there is a new ischemic change in the electrocardiogram; (3) new Q wave appears in the electrocardiogram; (4) imaging evidence suggests that newly-living myocardium is lost; (5) an intravascular thrombus is found by angiography or autopsy. Although the related regulation and control targets of myocardial infarction have been deeply researched, such as the inhibition of growth factor ligands, various receptors (platelet-derived growth factor receptors, vascular endothelial growth factor receptors and epidermal growth factor receptors) and various enzymes, the molecular targets for effectively diagnosing, preventing and treating myocardial infarction are still lacking, so that the search for the molecular markers of myocardial infarction is of great significance.
Disclosure of Invention
The invention aims to provide a molecular marker for diagnosing myocardial infarction.
In order to achieve the purpose, the invention adopts the following technical scheme:
in a first aspect, the invention provides a product for diagnosing myocardial infarction, which comprises an agent for detecting the expression level of TEX30 and/or ZNF420 gene.
In the present invention, TEX30 (Gene ID: 93081) includes TEX30 gene and its encoded protein and its homologues, mutations, and isoforms. The term encompasses full-length, unprocessed TEX30, as well as any form of TEX30 that results from processing in the cell. The term encompasses naturally occurring variants (e.g., splice variants or allelic variants) of TEX 30.
In the present invention, ZNF420 (gene ID: 147923) includes ZNF420 gene and its encoded protein and its homologue, mutation, and isoform. The term encompasses full length, unprocessed ZNF420, as well as any form of ZNF420 that results from processing in a cell. The term encompasses naturally occurring variants (e.g., splice variants or allelic variants) of ZNF 420.
The utility of the present invention is not limited to quantifying gene expression of any particular variant of the target gene of the present invention. It is known to those skilled in the art that when performing bioinformatic analysis, the sequenced sequence is usually aligned with a known gene, and the expression of the gene can be considered as long as the sequence can be aligned with the gene concerned, and therefore, when referring to differentially expressed genes, different transcripts, mutants or fragments thereof of the gene are also encompassed by the present invention.
It will be appreciated by those skilled in the art that the means by which gene expression is determined is not an important aspect of the present invention. The present invention may utilize any method known in the art to determine the expression level of a gene.
Further, the product comprises a nucleic acid membrane strip, a chip or a kit.
In the present invention, the nucleic acid membrane strip comprises a substrate and an oligonucleotide probe specifically recognizing TEX30 and/or ZNF420 immobilized on the substrate; the substrate may be any substrate suitable for immobilizing oligonucleotide probes, such as a nylon membrane, a nitrocellulose membrane, a polypropylene membrane, a glass plate, a silica gel wafer, a micro magnetic bead, or the like.
Further, the chip comprises a gene chip and a protein chip, wherein the gene chip comprises a primer or an oligonucleotide probe aiming at the TEX30 and/or the ZNF420, and the protein chip comprises a binding agent which specifically binds to the TEX30 and/or the ZNF420 protein.
Further, the kit comprises a gene detection kit and a protein detection kit, wherein the gene detection kit comprises a primer, an oligonucleotide probe or a chip specifically aiming at TEX30 and/or ZNF 420; the protein detection kit comprises a binding agent which specifically binds to TEX30 and/or ZNF420 protein.
The term "primer" refers to 7 to 50 nucleic acid sequences capable of forming a base pair (base pair) complementary to a template strand and serving as a starting point for replication of the template strand. The primers are generally synthesized, but naturally occurring nucleic acids may also be used. The sequence of the primer does not necessarily need to be completely identical to the sequence of the template, and may be sufficiently complementary to hybridize with the template. Additional features that do not alter the basic properties of the primer may be incorporated. Examples of additional features that may be incorporated include, but are not limited to, methylation, capping, substitution of more than one nucleic acid with a homolog, and modification between nucleic acids.
The term "hybridization" refers to the annealing of two complementary nucleic acid strands to one another under conditions of appropriate stringency. Hybridization is generally carried out using nucleic acid molecules of probe length. Nucleic acid hybridization techniques are well known in the art. Those skilled in the art know how to estimate and adjust the stringency of hybridization conditions such that sequences with at least the desired degree of complementarity will stably hybridize, while sequences with lower complementarity will not stably hybridize.
The term "probe" refers to a molecule that binds to a specific sequence or subsequence or other portion of another molecule. Unless otherwise indicated, the term "probe" generally refers to a polynucleotide probe that is capable of binding to another polynucleotide (often referred to as a "target polynucleotide") by complementary base pairing. Depending on the stringency of the hybridization conditions, a probe can bind to a target polynucleotide that lacks complete sequence complementarity to the probe. The probe may be directly or indirectly labeled, and includes within its scope a primer. Hybridization modes include, but are not limited to: solution phase, solid phase, mixed phase or in situ hybridization assays.
The term "oligonucleotide" refers to a short polymer composed of deoxyribonucleotides, ribonucleotides, or any combination thereof. The length of the oligonucleotide is typically between 10 nucleotides and about 100 nucleotides in length. The oligonucleotide is preferably from 15 nucleotides to 70 nucleotides in length, most typically from 20 nucleotides to 26 nucleotides. Oligonucleotides may be used as primers or probes.
In a second aspect, the present invention provides the use of an agent for detecting a molecular marker comprising TEX30 and/or ZNF420 in the manufacture of a product for the diagnosis of myocardial infarction.
Further, the reagent comprises a reagent for detecting the expression level of the TEX30 and/or ZNF420 gene in the sample by a sequencing technology, a nucleic acid hybridization technology, a nucleic acid amplification technology and a protein immunization technology.
The present invention can amplify the nucleic acid prior to or simultaneously with detection. Illustrative non-limiting examples of nucleic acid amplification techniques include, but are not limited to: polymerase Chain Reaction (PCR), reverse transcription polymerase chain reaction (RT-PCR), Transcription Mediated Amplification (TMA), Ligase Chain Reaction (LCR), Strand Displacement Amplification (SDA), and Nucleic Acid Sequence Based Amplification (NASBA). One of ordinary skill in the art will recognize that certain amplification techniques (e.g., PCR) require reverse transcription of RNA into DNA prior to amplification (e.g., RT-PCR), while other amplification techniques directly amplify RNA (e.g., TMA and NASBA).
Nucleic acid hybridization techniques of the invention include, but are not limited to, In Situ Hybridization (ISH), microarrays, and Southern or Northern blots. In Situ Hybridization (ISH) is a hybridization of specific DNA or RNA sequences in a tissue section or section using a labeled complementary DNA or RNA strand as a probe (in situ) or in the entire tissue if the tissue is small enough (whole tissue embedded ISH). DNA ISH can be used to determine the structure of chromosomes. RNA ISH is used to measure and locate mRNA and other transcripts (e.g., ncRNA) within tissue sections or whole tissue embedding. Sample cells and tissues are typically treated to fix the target transcript in situ and to increase probe access. The probe is hybridized to the target sequence at high temperature, and then excess probe is washed away. The localization and quantification of base-labeled probes in tissues labeled with radiation, fluorescence or antigens is performed using autoradiography, fluorescence microscopy or immunohistochemistry, respectively. ISH can also use two or more probes labeled with radioactive or other non-radioactive labels to detect two or more transcripts simultaneously.
Southern and Northern blots were used to detect specific DNA or RNA sequences, respectively. DNA or RNA extracted from the sample is fragmented, separated by electrophoresis on a matrix gel, and then transferred to a membrane filter. The filter-bound DNA or RNA is hybridized to a labeled probe complementary to the sequence of interest. Detecting the hybridization probes bound to the filter. A variation of this procedure is a reverse Northern blot, in which the substrate nucleic acid immobilized to the membrane is a collection of isolated DNA fragments and the probe is RNA extracted from the tissue and labeled.
Protein immunization techniques include sandwich immunoassays, such as sandwich ELISA, in which detection of a biomarker is performed using two antibodies that recognize different epitopes on the biomarker; radioimmunoassay (RIA), direct, indirect or contrast enzyme-linked immunosorbent assay (ELISA), Enzyme Immunoassay (EIA), Fluorescence Immunoassay (FIA), western blot, immunoprecipitation, and any particle-based immunoassay (e.g., using gold, silver or latex particles, magnetic particles, or quantum dots). The immunization can be carried out, for example, in the form of microtiter plates or strips.
Further, the reagent comprises:
oligonucleotide probes that specifically recognize the TEX30 and/or ZNF420 genes; or
Primers for specifically amplifying the TEX30 and/or ZNF420 genes; or
A binding agent that specifically binds to a protein encoded by a TEX30 and/or ZNF420 gene.
In a third aspect, the invention provides the use of molecular markers comprising TEX30 and/or ZNF420 in the construction of a computational model for predicting myocardial infarction.
In the present invention, the step of associating a marker level with a certain likelihood or risk may be carried out and carried out in different ways. Preferably, the measured concentrations of the gene and one or more other markers are mathematically combined and the combined value is correlated to the underlying diagnostic problem. The determination of marker values may be combined by any suitable prior art mathematical method.
Preferably, the mathematical algorithm applied in the marker combination is a logarithmic function. Preferably, the result of applying such a mathematical algorithm or such a logarithmic function is a single value. Such values can be readily correlated, in terms of underlying diagnostic problems, with, for example, an individual's risk of myocardial infarction or with other intentional diagnostic uses that help to assess patients with myocardial infarction. In a preferred manner, such a logarithmic function is obtained as follows: a) classifying individuals into groups, e.g., normal humans, individuals at risk of myocardial infarction, patients with myocardial infarction, etc., b) identifying markers that differ significantly between these groups by univariate analysis, c) log regression analysis to assess independent difference values of the markers that can be used to assess these different groups, and d) constructing a log function to combine the independent difference values. In this type of analysis, the markers are no longer independent, but represent a combination of markers.
The logarithmic function used to correlate marker combinations with disease preferably employs algorithms developed and obtained by applying statistical methods. For example, suitable statistical methods are Discriminant Analysis (DA) (i.e., linear, quadratic, regular DA), Kernel methods (i.e., SVM), nonparametric methods (i.e., k-nearest neighbor classifiers), PLS (partial least squares), tree-based methods (i.e., logistic regression, CART, random forest methods, boosting/bagging methods), generalized linear models (i.e., logistic regression), principal component-based methods (i.e., SIMCA), generalized additive models, fuzzy logic-based methods, neural network-and genetic algorithm-based methods. The skilled person will not have problems in selecting a suitable statistical method to evaluate the marker combinations of the invention and thereby obtain a suitable mathematical algorithm. In one embodiment, the statistical method used to obtain the mathematical algorithm used in assessing myocardial infarction is selected from DA (i.e., linear, quadratic, regular discriminant analysis), Kernel method (i.e., SVM), non-parametric method (i.e., k-nearest neighbor classifier), PLS (partial least squares), tree-based method (i.e., logistic regression, CART, random forest method, boosting method), or generalized linear model (i.e., logarithmic regression).
In a fourth aspect, the invention provides a pharmaceutical composition for treating myocardial infarction, which comprises an agent for inhibiting the expression of the TEX30 gene and/or an agent for promoting the expression of the ZNF420 gene.
In a fifth aspect, the invention provides the use of TEX30 and/or ZNF420 in the manufacture of a pharmaceutical composition for the treatment of myocardial infarction.
Further, the pharmaceutical composition comprises an agent that inhibits expression of the TEX30 gene and/or an agent that promotes expression of the ZNF420 gene.
The invention has the advantages and beneficial effects that:
the invention discloses a product for diagnosing myocardial infarction, and provides a new method for diagnosing myocardial infarction.
The invention also discloses a pharmaceutical composition for treating myocardial infarction.
Drawings
FIG. 1 is a TEX30 differential expression boxplot;
FIG. 2 is a ROC plot of TEX30 diagnosis of acute myocardial infarction;
FIG. 3 is a ROC graph of the combined diagnosis of acute myocardial infarction of TEX30 and ZNF 420.
Detailed Description
The technical solutions of the present invention are further illustrated by the following specific examples, which do not represent limitations to the scope of the present invention. Insubstantial modifications and adaptations of the present invention by others of the concepts fall within the scope of the invention.
Example 1 screening of differentially expressed genes in acute myocardial infarction
1. Data source
Downloading acute myocardial infarction (AIM) data set GSE66360 from GEO database, sample size control: AIM 50: 49.
2. Differential expression analysis
Differential expression analysis was performed using the "limma" package in R software, with screening criteria for differential genes as adj. p value < 0.05.
3. Results of the experiment
The analysis result shows that the biomarker TEX30 related to the invention is up-regulated in a sample of an acute myocardial infarction patient, and ZNF420 is down-regulated in a sample of an acute myocardial infarction patient, as shown in Table 1 and FIG. 1.
TABLE 1 differential expression of TEX30, ZNF420
Gene AveExpr t P.Value
TEX30 7.61 4.28 0.00
ZNF420 7.26 -5.69 0.00
Example 2 diagnostic Performance validation
1. Experimental methods
Receiver Operating Curves (ROCs) were plotted using the R package "pROC" (version 1.15.0), AUC values, sensitivity and specificity were analyzed, and the diagnostic efficacy of the markers alone or in combination was judged. When the diagnosis efficiency of the index combination is judged, logistic regression is carried out on the expression level of each gene, the probability of whether each individual suffers from cancer is calculated through a fitted regression curve, different probability division threshold values are determined, and the sensitivity, specificity, accuracy and the like of the combined detection scheme are calculated according to the determined probability division threshold values.
2. Results of the experiment
(1) ROC Curve analysis of TEX30
Referring to table 2 and fig. 2, the diagnosis efficacy of TEX30 indicates that TEX30 has a good diagnosis effect on acute myocardial infarction.
TABLE 2 diagnostic efficacy of TEX30
Gene AUC Sensitivity of the composition Specificity of
TEX30 0.74 0.64 0.78
(2) ROC curve analysis for TEX30+ ZNF420 combined diagnosis
The AUC values of TEX30 and ZNF420 genes are shown in Table 3, and the ROC curve of the TEX30+ ZNF420 combined diagnosis is shown in FIG. 3.
TABLE 3 AUC values of genes
Gene AUC
TEX30 0.74
ZNF420 0.79
TEX30+ZNF420 0.92
According to the experimental results, the diagnosis effect of the TEX30+ ZNF420 combination on acute myocardial infarction is better than that of a single marker, and the diagnosis effect is better.
The above description of the embodiments is only intended to illustrate the method of the invention and its core idea. It should be noted that, for those skilled in the art, without departing from the principle of the present invention, several improvements and modifications can be made to the present invention, and these improvements and modifications will also fall into the protection scope of the claims of the present invention.

Claims (10)

1. A product for diagnosing myocardial infarction, which comprises an agent for detecting the expression level of TEX30 and/or ZNF420 gene.
2. The product of claim 1, wherein the product comprises a nucleic acid membrane strip, chip or kit.
3. The product as claimed in claim 2, wherein the chip comprises a gene chip comprising primers or oligonucleotide probes for TEX30 and/or ZNF420, a protein chip comprising a binding agent that specifically binds to TEX30 and/or ZNF420 proteins.
4. The product of claim 2, wherein the kit comprises a gene detection kit and a protein detection kit, wherein the gene detection kit comprises primers, oligonucleotide probes or chips specific for TEX30 and/or ZNF 420; the protein detection kit comprises a binding agent which specifically binds to TEX30 and/or ZNF420 protein.
5. Use of a reagent for detecting a molecular marker comprising TEX30 and/or ZNF420 in the manufacture of a product for the diagnosis of myocardial infarction.
6. The use as claimed in claim 5 wherein the reagents include reagents for detecting the expression level of the TEX30 and/or ZNF420 genes in the sample by sequencing techniques, nucleic acid hybridisation techniques, nucleic acid amplification techniques, protein immunisation techniques.
7. The use according to claim 5 or 6, wherein said agent comprises:
oligonucleotide probes that specifically recognize the TEX30 and/or ZNF420 genes; or
Primers for specifically amplifying the TEX30 and/or ZNF420 genes; or
A binding agent that specifically binds to a protein encoded by a TEX30 and/or ZNF420 gene.
8. Use of a molecular marker in the construction of a computational model for predicting myocardial infarction, wherein the molecular marker comprises TEX30 and/or ZNF 420.
9. A pharmaceutical composition for use in the treatment of myocardial infarction, said pharmaceutical composition comprising an agent that inhibits the expression of TEX30 gene and/or an agent that promotes the expression of ZNF420 gene.
Use of TEX30 and/or ZNF420 in the manufacture of a pharmaceutical composition for the treatment of myocardial infarction, preferably wherein the pharmaceutical composition comprises an agent which inhibits the expression of the TEX30 gene and/or an agent which promotes the expression of the ZNF420 gene.
CN202110307455.8A 2021-03-23 2021-03-23 Myocardial infarction differential expression gene and application thereof Pending CN112760372A (en)

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Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN105400880A (en) * 2015-12-11 2016-03-16 天津市人民医院 Acute myocardial infarction early diagnosis marker
CN108624680A (en) * 2018-07-03 2018-10-09 北京泱深生物信息技术有限公司 The application of RAE1 genes or albumen as the biomarker of diagnosing myocardial infarction
CN108913769A (en) * 2018-07-26 2018-11-30 泰山医学院 Early diagnose the molecular marker of myocardial infarction

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN105400880A (en) * 2015-12-11 2016-03-16 天津市人民医院 Acute myocardial infarction early diagnosis marker
CN108624680A (en) * 2018-07-03 2018-10-09 北京泱深生物信息技术有限公司 The application of RAE1 genes or albumen as the biomarker of diagnosing myocardial infarction
CN108913769A (en) * 2018-07-26 2018-11-30 泰山医学院 Early diagnose the molecular marker of myocardial infarction

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