WO2021112619A1 - Marqueurs génétiques multiples pour prédire le risque de développer des maladies provoquées par une immunité réduite et procédé pour prédire le risque de développer des maladies à l'aide de ceux-ci - Google Patents

Marqueurs génétiques multiples pour prédire le risque de développer des maladies provoquées par une immunité réduite et procédé pour prédire le risque de développer des maladies à l'aide de ceux-ci Download PDF

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WO2021112619A1
WO2021112619A1 PCT/KR2020/017641 KR2020017641W WO2021112619A1 WO 2021112619 A1 WO2021112619 A1 WO 2021112619A1 KR 2020017641 W KR2020017641 W KR 2020017641W WO 2021112619 A1 WO2021112619 A1 WO 2021112619A1
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cancer
mir
disease
immunity
predicting
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English (en)
Korean (ko)
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박영광
임장미
전윤경
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주식회사 레피겐엠디
서울대학교병원
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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
    • 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
    • C12Q1/6886—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
    • 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
    • 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
    • C12Q2600/178—Oligonucleotides characterized by their use miRNA, siRNA or ncRNA

Definitions

  • the present invention relates to predicting the risk of disease development due to reduced immunity.
  • the human body has various defense systems to protect the body from foreign invaders. Among them, it has an immune system that protects the body from disease and restores it to its original state. This immune system accurately distinguishes between self and non-self and does not induce an immune response to itself, but induces an immune response to others to suppress the onset of disease.
  • the body's immune system to defend against foreign invaders can be divided into an innate immune system (natural immunity) and an acquired immune system (acquired immunity or adaptive immunity).
  • Innate immunity is responsible for the immediate defense against foreign invaders. It kills or secretes toxic substances using receptors that recognize structures specific to foreign invaders.
  • Representative cells constituting this immune system include neutrophils, macrophages, and natural killer cells (NK cells).
  • acquired (acquired) immunity is the immune system produced by the body by a specific antigen. This immunity includes T-cells, B-cells, antibodies, and the like. By inducing the production of various cytokines by the interaction of these cells, they are responsible for defense, but acquired immunity declines with age.
  • inflammatory response is a type of non-specific immune response.
  • Acute inflammation naturally disappears over time, but chronic inflammation is caused by the continuous repetition of micro-inflammation, which encourages abnormalities in the body and acts as a cause of the onset of various diseases.
  • Chronic inflammation can be the trigger for all diseases, but it is left unattended because there are no obvious symptoms.
  • chronic inflammation is closely related to the occurrence, progression, and severity of various diseases, including metabolic syndrome, heart failure, renal failure, and dementia and cancer.
  • the ability to deal with inflammation decreases, which leads to chronic inflammation.
  • cancer cells that are formed by changing their own cells also recognize non-self, such as producing a protein different from the original “self” due to a genetic abnormality provokes an immune response.
  • cancer immunity if cancer cells learn this immune evasion method, immune escape occurs and cancer develops.
  • cancer cells it is very natural that cancer cells are generated, and a series of processes that detect the cancer cells and kill the cancer cells occur.
  • cancer cells use immune escape, these cancer cells evade the attack of immune cells and grow into cancer cells, causing problems.
  • T-cells T-cells, B-cells, natural killer cells, macrophages
  • T-cells T-cells, B-cells, natural killer cells, macrophages
  • the present inventors selected miRNAs involved in regulating the immune response, in particular, the expression of cytokines, and confirmed that when the expression level of the miRNA is increased or decreased, the risk of developing diseases due to decreased immunity is increased. , the present invention was completed.
  • a multi-gene marker composition for predicting increased risk for disease development due to reduced immunity comprising one or more miRNAs selected from the group consisting of miR-146a, miR-155 and miR-454 will do
  • Another object of the present invention is to predict an increased risk of developing a disease due to reduced immunity, including an agent for measuring the expression level of one or more miRNAs selected from the group consisting of miR-146a, miR-155 and miR-454. to provide a composition.
  • Another object of the present invention is to provide a kit for predicting an increased risk for the onset of a disease due to reduced immunity, comprising the composition according to the present invention.
  • Another object of the present invention is to provide an information providing method for predicting an increased risk of developing a disease due to a decrease in immunity of a subject.
  • the present invention includes one or more miRNAs selected from the group consisting of miR-146a, miR-155 and miR-454, for predicting increased risk for the onset of disease due to reduced immunity.
  • miRNAs selected from the group consisting of miR-146a, miR-155 and miR-454, for predicting increased risk for the onset of disease due to reduced immunity.
  • Genetic marker compositions are provided.
  • the present invention provides a composition for predicting an increased risk of developing a disease due to reduced immunity, comprising an agent for measuring the expression level of one or more miRNAs selected from the group consisting of miR-146a, miR-155 and miR-454 provides
  • the agent may be a primer or probe that specifically binds to one or more of the miRNAs, but is not limited thereto.
  • the present invention provides a kit for predicting an increased risk for the onset of a disease due to reduced immunity, comprising the composition according to the present invention.
  • the present invention provides a method for predicting an increased risk for the onset of a disease due to a decrease in immunity of a subject or an information providing method for predicting the risk, comprising the steps of:
  • the sample is any one selected from the group consisting of blood, serum, plasma, saliva, biopsy, tumor tissue, liquid culture, feces and urine derived from a subject. may be, but is not limited thereto.
  • the expression level of the miRNA is measured using a reverse transcriptase polymerase reaction, a competitive reverse transcriptase polymerase reaction, a real-time reverse transcriptase polymerase reaction, an RNase protection assay, Northern blotting or a gene chip.
  • a reverse transcriptase polymerase reaction a competitive reverse transcriptase polymerase reaction
  • a real-time reverse transcriptase polymerase reaction a real-time reverse transcriptase polymerase reaction
  • an RNase protection assay e.g., Northern blotting or a gene chip.
  • the disease caused by the decrease in immunity may be selected from the group consisting of cancer, autoimmune disease, metabolic disease, and infectious disease, but is not limited thereto.
  • the cancer is lung cancer, liver cancer, stomach cancer, esophageal cancer, colorectal cancer, pancreatic cancer, gallbladder cancer, biliary tract cancer, breast cancer, prostate cancer, bladder cancer, thyroid cancer, kidney cancer, cervical cancer, ovarian cancer, skin cancer , hematological cancer, lymphoma, glioma, colon cancer and osteosarcoma, but is not limited thereto.
  • the present invention also provides the use of a composition comprising one or more miRNAs selected from the group consisting of miR-146a, miR-155 and miR-454 for predicting an increased risk of developing a disease due to reduced immunity. .
  • the present invention can be very effectively utilized for the prevention and management of diseases, which is expected to greatly contribute to the reduction of medical expenses at the national level as well as the individual.
  • FIG. 1 is a diagram comparing the relative expression of multiple genetic markers according to the present invention in a sample of a normal person and a patient with six major cancers.
  • BC breast cancer
  • CC colorectal cancer
  • HCC liver cancer
  • PC prostate cancer
  • LC lung cancer
  • SC stomach cancer
  • 2A is a diagram comparing the relative expression of multiple genetic markers according to the present invention in samples from normal subjects and stage 1 and stage 2 cancer patients.
  • Figure 2b is a diagram comparing the change in the production of IFN- ⁇ for a sample of a normal person and six cancer patients.
  • 3 is a diagram comparing the expression changes of miR-146a, miR-155 and miR-454 after inducing the proliferation of immune cells in peripheral blood mononuclear cells.
  • the present inventors have completed the present invention by selecting miRNAs involved in regulating the immune response and confirming that the risk of disease due to reduced immunity increases when the expression level of the miRNA is increased or decreased.
  • multiple genetic markers are selected for predicting the risk of disease due to reduced immunity by measuring immune activity, and for the final selected miR-146a, miR-155 and miR-454, normal As a result of analyzing the expression level of the gene in the samples of the six major cancer patients, it was confirmed that one or more of the three genes exhibited a statistically significant level of expression change pattern (see Examples 1 and 2). ).
  • the change in the expression of multiple genetic markers according to the present invention may cause a wider range of diseases It has been demonstrated that prediction is possible (see Example 3).
  • the multiple genetic markers miR-146a, miR-155 and miR-454 are modulators directly related to the regulation of immune responses through an immune response induction experiment in peripheral blood mononuclear cells. , thus proving that an increased risk of developing a disease in the future can be predicted by measuring the expression change of the multiple genetic markers (see Example 4).
  • the present invention provides a multigene marker composition for predicting an increased risk of developing a disease due to reduced immunity, comprising one or more miRNAs selected from the group consisting of miR-146a, miR-155 and miR-454.
  • miR-146a refers to hsa-miR-146a-5p (miR base Accession number: MIMAT0000449) of a mature sequence, and may consist of the following nucleotide sequence.
  • miR-155 refers to hsa-miR-155-5p (miR base Accession number: MIMAT0000646) of a mature sequence, and may consist of the following nucleotide sequence.
  • miR-454 refers to hsa-miR-454-3p (miR base Accession number: MIMAT0003885) of a mature sequence, and may consist of the following nucleotide sequence.
  • onset risk may be a relative risk of developing a disease due to reduced immunity.
  • the risk may indicate whether the probability of developing the disease is increased or decreased compared to a healthy normal group.
  • the present invention includes an agent for measuring the expression level of one or more miRNAs selected from the group consisting of miR-146a, miR-155 and miR-454. Increase in the onset of diseases due to reduced immunity.
  • a composition for predicting risk is provided.
  • the agent may be a primer or probe that specifically binds to one or more of the miRNAs, but the form is not limited as long as it is for measuring the expression level of the miRNA.
  • change in the expression level of a gene means that the expression level of a specific gene in the experimental group is statistically significantly “increased” or “decreased” compared to the expression level in the control group. .
  • “statistically significant level of expression change” may mean that the expression level of a specific gene in the experimental group is reduced by 5% or more compared to the expression level in the control group.
  • the decrease in the expression level to a statistically significant degree indicates that the expression level of a specific gene in the experimental group is 5 to 100%, 10 to 100%, 15 to 100%, 20 to 100%, 25 compared to the expression level in the control group. to 100%, 30 to 100%, 35 to 100%, 40 to 100%, 45 to 100%, 50 to 100%, 55 to 100%, 60 to 100%, 65 to 100%, 70 to 100%, 75 to 100%, 80 to 100%, 85 to 100%, 90 to 100%, or 95 to 100% may be reduced, but is not limited thereto.
  • a statistically significant level of expression change may mean that the expression level of a specific gene in the experimental group is increased by 5% or more compared to the expression level in the control group.
  • an increase in the expression level to a statistically significant degree indicates that the expression level of a specific gene in the experimental group is 5 to 100%, 10 to 100%, 15 to 100%, 20 to 100%, compared to the expression level in the control group. 100%, 25-100%, 30-100%, 35-100%, 40-100%, 45-100%, 50-100%, 55-100%, 60-100%, 65-100%, 70- 100%, 75 to 100%, 80 to 100%, 85 to 100%, 90 to 100%, or 95 to 100%, or may be increased by 100% or more, but is not limited thereto.
  • primer refers to an oligonucleotide synthesized for use in diagnosis, DNA sequencing, etc. as a short gene sequence serving as a starting point of DNA synthesis.
  • the primers can be synthesized and used with a length of typically 15 to 30 base pairs, but may vary depending on the purpose of use, and may be modified by methylation, capping, etc. by a known method.
  • Primers are capable of initiating DNA synthesis in the presence of reagents for polymerization (ie, DNA polymerase or reverse transcriptase) and four different nucleoside triphosphates in appropriate buffers and temperatures.
  • probe refers to a nucleic acid capable of specifically binding to RNA having a length of several bases to several hundreds of bases produced through enzymatic chemical separation and purification or synthesis.
  • the presence or absence of RNA can be checked by labeling radioactive isotopes or enzymes, and can be designed and modified by a known method.
  • the present invention provides a kit for predicting increased risk for the onset of disease due to reduced immunity, comprising the composition according to the present invention.
  • the present invention provides a method for predicting an increased risk for the onset of a disease due to a decrease in immunity of a subject or an information providing method for predicting the risk, comprising the steps of:
  • the subject is an animal, preferably a mammal, for example, a human, a mouse, a rat, a cow, a sheep, a dog, a cat, a monkey, apes, etc. whose risk of developing a disease due to reduced immunity is to be predicted. may include, but is not limited to.
  • the sample may be naturally or artificially separated from the subject, for example, blood, serum, plasma, saliva, biopsy, tumor tissue, liquid culture, feces, It may be urine, etc., preferably plasma, but is not limited thereto.
  • the sample may be appropriately collected from the subject according to a known method, and may be subjected to a necessary pre-treatment according to the detection method.
  • the time point at which the sample is collected from the subject may be before or after the onset of the disease, but preferably, the sample may be collected before the onset of the disease.
  • the expression level of the miRNA can be measured using a reverse transcriptase polymerase reaction, a competitive reverse transcriptase polymerase reaction, a real-time reverse transcriptase polymerase reaction, an RNase protection assay, Northern blotting or a gene chip, but miRNA If the expression level of the can be measured, it is not limited to the methods listed above.
  • the disease caused by the decrease in immunity may be cancer, autoimmune disease, metabolic disease, infectious disease, etc., but is not limited thereto.
  • the cancer is lung cancer, liver cancer, stomach cancer, esophageal cancer, colorectal cancer, pancreatic cancer, gallbladder cancer, biliary tract cancer, breast cancer, prostate cancer, bladder cancer, thyroid cancer, kidney cancer, cervical cancer, ovarian cancer, skin cancer, blood cancer, lymphoma , glioma, colon cancer, osteosarcoma, etc., but is not limited thereto.
  • the metabolic disease may be diabetes, hypoglycemia, hypercholesterolemia, hemochromatosis, hereditary disease, porphyria, etc., but is not limited thereto.
  • the infectious disease is a disease caused by infection of a virus or pathogen, and is a concept including all diseases that can be transmitted and infected through respiratory, blood, skin contact, etc.
  • infectious diseases include hepatitis B and C, human papilloma virus (HPV) infection, cytomegalovirus infection, viral respiratory disease, influenza, etc., but are limited thereto no.
  • RNA in exosomes from plasma of normal people and cancer patients was performed according to the manufacturer's instructions using a reagent (Genolusion Co., Ltd., Korea). Extraction of RNA in exosomes from plasma separated only RNA from proteins, DNA, and RNA (mRNA, miRNA, rRNA, etc.) flowing out of exosomes after lysis of exosomes in plasma. At this time, an extraction protocol was established that was optimized so that the protein and DNA were not contaminated to increase the purity and maximize the RNAs extraction concentration (RNA prep yield).
  • RNA concentration in the exosomes extracted from plasma was measured using a nano-drop (absorbance at 260 nm wavelength). RNA purity and contamination level were checked through 260/280 ratio and 260/230 ratio, and RNA within the normal range was used for the experiment.
  • Two-step qRT-PCR was performed using 10 ng of exo RNA extracted from plasma as a template.
  • the PCR equipment was StepOne plus (ABI, USA), and all samples were performed in duplicate to increase the reliability of the results.
  • IFN- ⁇ concentration in plasma of the specimen was measured using a human IFN- ⁇ immunoassay kit (R&D, USA).
  • a plate coated with a capture antibody was blocked on another surface for specific binding to a sample antigen.
  • a detection antibody labeled with biotin was bound.
  • HRP horseradish peroxidase
  • the present inventors conducted screening focusing on miRs related to immune activity in order to select candidate gene markers for predicting the risk of disease due to reduced immunity by measuring immune activity.
  • cytokines, IFN- ⁇ , TNF- ⁇ , IL-2, IL-6, IL-8, etc. which are involved in the activity of T cells
  • NK cells NK cells
  • macrophages which are representative immune cells involved in the development of disease miRNAs involved in regulating the expression of miRNAs were screened, and candidate miRNAs were first selected.
  • binding sites in the mRNA UTR (Untranslated region) region were identified using target prediction databases, microRNA.org and TargetScan.
  • miRNAs screened from the above process 6 genes were selected as secondary candidates for miRNAs with known functions involved in the generation and progression of cancer cells.
  • the onco-miR gene involved in cancer induction and the tumor suppressor miR gene involved in cancer suppression were considered together.
  • miR-146a, miR-155, miR-186, miR-454, miR-301a/b and miR-181a were selected as candidate genes.
  • the multi-gene markers miR-146a, miR-155 and miR-454 finally selected for the measurement of immune activity, normal persons and six major cancers - breast cancer (BC), colorectal cancer (CC), liver cancer (HCC), prostate cancer ( PC), lung cancer (LC) and gastric cancer (SC)—the expression level of the gene was analyzed in patient samples.
  • BC breast cancer
  • CC colorectal cancer
  • HCC liver cancer
  • PC prostate cancer
  • SC gastric cancer
  • Example 3 Comparative analysis of expression of multiple genetic markers and IFN- ⁇ expression
  • the present inventors compared with the IFN- ⁇ production analysis, which is a method for measuring only NK cell activity among various immune cells as a conventional method for measuring immune activity, the multiple genetic markers, miR-146a, miR-155 and miR- according to the present invention.
  • IFN- ⁇ production analysis which is a method for measuring only NK cell activity among various immune cells as a conventional method for measuring immune activity, the multiple genetic markers, miR-146a, miR-155 and miR- according to the present invention.
  • a comparative analysis experiment was conducted on samples from the same cancer patient.
  • the change in IFN- ⁇ production showed a statistically significant level difference in only two of the six carcinomas ( FIG. 2B ), whereas the multi-gene marker according to the present invention was used in all six types of cancers ( FIG. 2B ). It was confirmed that one or more genes showed a statistically significant level of change in carcinoma ( FIG. 2A ).
  • the above results prove that the change in the expression of the multiple genetic markers according to the present invention has greater clinical significance as a high-risk selection marker that can cause a wider range of diseases than the change in IFN- ⁇ production.
  • Example 4 Analysis of changes in expression of multiple genetic markers according to the inhibition and activity of immune cells
  • the present invention is the development of disease It was intended to prove that it is valid for risk prediction.
  • an immune cell proliferation inducer for peripheral blood mononuclear cells isolated from normal human blood. was treated to analyze the expression change.
  • Peripheral blood mononuclear cells PBMCs
  • PBMCs peripheral blood mononuclear cells
  • T cells lymphocytes
  • monocytes monocytes
  • B cells B cells
  • the multiple genetic markers miR-146a, miR-155 and miR-454 according to the present invention can be viewed as modulators directly related to immune regulation, and thus the expression change of the multiple genetic markers is measured. By doing so, it is possible to predict an increased risk of developing a disease in the future.
  • the present invention can be very effectively utilized for the prevention and management of diseases, which is expected to greatly contribute to the reduction of medical expenses at the national level as well as the individual.

Abstract

La présente invention concerne des marqueurs génétiques multiples pour prédire un risque accru de développer des maladies provoquées par une immunité réduite, y compris divers types de cancer. Plus particulièrement, la présente invention concerne : une composition de marqueurs génétiques multiples pour prédire un risque accru de développer des maladies provoquées par une immunité réduite, la composition comprenant un ou plusieurs miARN sélectionnés dans le groupe constitué par miR-146a, miR-155 et miR-454 ; une composition pour prédire un risque accru de développer des maladies provoquées par une immunité réduite, la composition comprenant un agent destiné à mesurer le niveau d'expression de marqueurs génétiques multiples ; et analogue(s), ladite composition pouvant ainsi être utilisée de manière très efficace dans la prévention et la prise en charge de maladies.
PCT/KR2020/017641 2019-12-06 2020-12-04 Marqueurs génétiques multiples pour prédire le risque de développer des maladies provoquées par une immunité réduite et procédé pour prédire le risque de développer des maladies à l'aide de ceux-ci WO2021112619A1 (fr)

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KR10-2019-0161350 2019-12-06
KR10-2020-0093453 2019-12-06
KR1020190161350 2019-12-06
KR1020200093453A KR102288359B1 (ko) 2019-12-06 2020-07-28 면역력 감소에 의한 질병의 발병 위험 예측용 다중 유전자 마커 및 이를 이용한 질병의 발병 위험 예측 방법

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Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2336353A1 (fr) * 2009-12-17 2011-06-22 febit holding GmbH Empreinte miARN dans le diagnostic des maladies
US20110151430A1 (en) * 2007-09-06 2011-06-23 University Of Massachusetts VIRUS-SPECIFIC miRNA SIGNATURES FOR DIAGNOSIS AND THERAPEUTIC TREATMENT OF VIRAL INFECTION
EP2354246A1 (fr) * 2010-02-05 2011-08-10 febit holding GmbH ARNm dans le diagnostic du cancer ovarien
US20130142728A1 (en) * 2011-10-27 2013-06-06 Asuragen, Inc. Mirnas as diagnostic biomarkers to distinguish benign from malignant thyroid tumors
KR20170035932A (ko) * 2014-08-07 2017-03-31 에이전시 포 사이언스, 테크놀로지 앤드 리서치 위암 진단용 microrna 바이오마커

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2341145A1 (fr) * 2009-12-30 2011-07-06 febit holding GmbH Empreinte ARNm dans le diagnostic de maladies

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20110151430A1 (en) * 2007-09-06 2011-06-23 University Of Massachusetts VIRUS-SPECIFIC miRNA SIGNATURES FOR DIAGNOSIS AND THERAPEUTIC TREATMENT OF VIRAL INFECTION
EP2336353A1 (fr) * 2009-12-17 2011-06-22 febit holding GmbH Empreinte miARN dans le diagnostic des maladies
EP2354246A1 (fr) * 2010-02-05 2011-08-10 febit holding GmbH ARNm dans le diagnostic du cancer ovarien
US20130142728A1 (en) * 2011-10-27 2013-06-06 Asuragen, Inc. Mirnas as diagnostic biomarkers to distinguish benign from malignant thyroid tumors
KR20170035932A (ko) * 2014-08-07 2017-03-31 에이전시 포 사이언스, 테크놀로지 앤드 리서치 위암 진단용 microrna 바이오마커

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