CN113866415B - Diagnostic and prognostic markers for breast cancer brain metastasis - Google Patents
Diagnostic and prognostic markers for breast cancer brain metastasis Download PDFInfo
- Publication number
- CN113866415B CN113866415B CN202111191448.2A CN202111191448A CN113866415B CN 113866415 B CN113866415 B CN 113866415B CN 202111191448 A CN202111191448 A CN 202111191448A CN 113866415 B CN113866415 B CN 113866415B
- Authority
- CN
- China
- Prior art keywords
- breast cancer
- gene
- brain metastasis
- marker
- cancer brain
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 206010006187 Breast cancer Diseases 0.000 title claims abstract description 41
- 208000026310 Breast neoplasm Diseases 0.000 title claims abstract description 41
- 206010027476 Metastases Diseases 0.000 title claims abstract description 34
- 230000009401 metastasis Effects 0.000 title claims abstract description 34
- 210000004556 brain Anatomy 0.000 title claims abstract description 32
- 108090000623 proteins and genes Proteins 0.000 claims abstract description 67
- 239000003550 marker Substances 0.000 claims abstract description 22
- 239000003153 chemical reaction reagent Substances 0.000 claims abstract description 20
- 102000004169 proteins and genes Human genes 0.000 claims abstract description 18
- 238000004393 prognosis Methods 0.000 claims abstract description 13
- 102100039126 5-hydroxytryptamine receptor 7 Human genes 0.000 claims abstract description 11
- 102000017906 ADRA2A Human genes 0.000 claims abstract description 9
- 102000017918 ADRB3 Human genes 0.000 claims abstract description 9
- 108060003355 ADRB3 Proteins 0.000 claims abstract description 9
- 101000756842 Homo sapiens Alpha-2A adrenergic receptor Proteins 0.000 claims abstract description 9
- 101000744211 Homo sapiens 5-hydroxytryptamine receptor 7 Proteins 0.000 claims abstract 2
- 239000000523 sample Substances 0.000 claims description 11
- 101000678746 Homo sapiens Acetylcholine receptor subunit beta Proteins 0.000 claims description 10
- 102100022725 Acetylcholine receptor subunit beta Human genes 0.000 claims description 9
- 102000017677 HTR3C Human genes 0.000 claims description 8
- 101000964063 Homo sapiens 5-hydroxytryptamine receptor 3C Proteins 0.000 claims description 8
- 238000003745 diagnosis Methods 0.000 abstract description 9
- 101000745163 Homo sapiens Neuronal acetylcholine receptor subunit alpha-3 Proteins 0.000 abstract description 3
- 230000002596 correlated effect Effects 0.000 abstract description 3
- 102100039908 Neuronal acetylcholine receptor subunit alpha-3 Human genes 0.000 abstract description 2
- 230000009286 beneficial effect Effects 0.000 abstract description 2
- 230000014509 gene expression Effects 0.000 description 15
- 235000018102 proteins Nutrition 0.000 description 14
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 12
- 230000004083 survival effect Effects 0.000 description 8
- 102000005962 receptors Human genes 0.000 description 7
- 108020003175 receptors Proteins 0.000 description 7
- 108060003345 Adrenergic Receptor Proteins 0.000 description 5
- 102000017910 Adrenergic receptor Human genes 0.000 description 5
- 238000001514 detection method Methods 0.000 description 5
- 230000036962 time dependent Effects 0.000 description 5
- 102100030913 Acetylcholine receptor subunit alpha Human genes 0.000 description 4
- 101000726895 Homo sapiens Acetylcholine receptor subunit alpha Proteins 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 239000012528 membrane Substances 0.000 description 4
- 238000000034 method Methods 0.000 description 4
- 208000003174 Brain Neoplasms Diseases 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- 206010059282 Metastases to central nervous system Diseases 0.000 description 3
- 108020004101 alpha-2 Adrenergic Receptor Proteins 0.000 description 3
- 102000030484 alpha-2 Adrenergic Receptor Human genes 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 102000039446 nucleic acids Human genes 0.000 description 3
- 108020004707 nucleic acids Proteins 0.000 description 3
- 150000007523 nucleic acids Chemical class 0.000 description 3
- 238000003752 polymerase chain reaction Methods 0.000 description 3
- 229940076279 serotonin Drugs 0.000 description 3
- 210000002820 sympathetic nervous system Anatomy 0.000 description 3
- 102000040125 5-hydroxytryptamine receptor family Human genes 0.000 description 2
- 108091032151 5-hydroxytryptamine receptor family Proteins 0.000 description 2
- 238000002965 ELISA Methods 0.000 description 2
- 238000008157 ELISA kit Methods 0.000 description 2
- 102000003688 G-Protein-Coupled Receptors Human genes 0.000 description 2
- 108090000045 G-Protein-Coupled Receptors Proteins 0.000 description 2
- 102000004108 Neurotransmitter Receptors Human genes 0.000 description 2
- 108090000590 Neurotransmitter Receptors Proteins 0.000 description 2
- 102000019315 Nicotinic acetylcholine receptors Human genes 0.000 description 2
- 108050006807 Nicotinic acetylcholine receptors Proteins 0.000 description 2
- 239000000020 Nitrocellulose Substances 0.000 description 2
- 239000004677 Nylon Substances 0.000 description 2
- 102000018120 Recombinases Human genes 0.000 description 2
- 108010091086 Recombinases Proteins 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 102000030621 adenylate cyclase Human genes 0.000 description 2
- 108060000200 adenylate cyclase Proteins 0.000 description 2
- 239000002131 composite material Substances 0.000 description 2
- 230000000875 corresponding effect Effects 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- 239000005556 hormone Substances 0.000 description 2
- 229940088597 hormone Drugs 0.000 description 2
- 230000003100 immobilizing effect Effects 0.000 description 2
- 238000011901 isothermal amplification Methods 0.000 description 2
- 230000003902 lesion Effects 0.000 description 2
- 210000002569 neuron Anatomy 0.000 description 2
- 239000002858 neurotransmitter agent Substances 0.000 description 2
- 229920001220 nitrocellulos Polymers 0.000 description 2
- 229920001778 nylon Polymers 0.000 description 2
- 229920000642 polymer Polymers 0.000 description 2
- 238000001959 radiotherapy Methods 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 101150090724 3 gene Proteins 0.000 description 1
- 102100040368 5-hydroxytryptamine receptor 6 Human genes 0.000 description 1
- 101710150237 5-hydroxytryptamine receptor 7 Proteins 0.000 description 1
- 101150101112 7 gene Proteins 0.000 description 1
- 101100097467 Arabidopsis thaliana SYD gene Proteins 0.000 description 1
- 206010003805 Autism Diseases 0.000 description 1
- 208000020706 Autistic disease Diseases 0.000 description 1
- 102000014914 Carrier Proteins Human genes 0.000 description 1
- 102000016928 DNA-directed DNA polymerase Human genes 0.000 description 1
- 108010014303 DNA-directed DNA polymerase Proteins 0.000 description 1
- 108091006027 G proteins Proteins 0.000 description 1
- 102000030782 GTP binding Human genes 0.000 description 1
- 108091000058 GTP-Binding Proteins 0.000 description 1
- -1 HTR7 Proteins 0.000 description 1
- 101000964051 Homo sapiens 5-hydroxytryptamine receptor 6 Proteins 0.000 description 1
- 238000007397 LAMP assay Methods 0.000 description 1
- 102000004086 Ligand-Gated Ion Channels Human genes 0.000 description 1
- 108090000543 Ligand-Gated Ion Channels Proteins 0.000 description 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
- 208000004059 Male Breast Neoplasms Diseases 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 238000000636 Northern blotting Methods 0.000 description 1
- 101100495925 Schizosaccharomyces pombe (strain 972 / ATCC 24843) chr3 gene Proteins 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 210000000577 adipose tissue Anatomy 0.000 description 1
- 210000002934 adrenergic neuron Anatomy 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 102000012740 beta Adrenergic Receptors Human genes 0.000 description 1
- 108010079452 beta Adrenergic Receptors Proteins 0.000 description 1
- 108091008324 binding proteins Proteins 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 230000000747 cardiac effect Effects 0.000 description 1
- 230000009084 cardiovascular function Effects 0.000 description 1
- 150000003943 catecholamines Chemical class 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 1
- 230000002999 depolarising effect Effects 0.000 description 1
- 238000006073 displacement reaction Methods 0.000 description 1
- 238000001962 electrophoresis Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- 210000002216 heart Anatomy 0.000 description 1
- 238000009396 hybridization Methods 0.000 description 1
- 238000003384 imaging method Methods 0.000 description 1
- 238000011532 immunohistochemical staining Methods 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 238000012417 linear regression Methods 0.000 description 1
- 230000004130 lipolysis Effects 0.000 description 1
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 1
- 238000001294 liquid chromatography-tandem mass spectrometry Methods 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 201000005202 lung cancer Diseases 0.000 description 1
- 208000020816 lung neoplasm Diseases 0.000 description 1
- 210000002751 lymph Anatomy 0.000 description 1
- 201000003175 male breast cancer Diseases 0.000 description 1
- 208000010907 male breast carcinoma Diseases 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 230000001394 metastastic effect Effects 0.000 description 1
- 206010061289 metastatic neoplasm Diseases 0.000 description 1
- 239000003226 mitogen Substances 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 230000002474 noradrenergic effect Effects 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 210000004224 pleura Anatomy 0.000 description 1
- 230000003518 presynaptic effect Effects 0.000 description 1
- 238000003127 radioimmunoassay Methods 0.000 description 1
- 238000000611 regression analysis Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 238000012502 risk assessment Methods 0.000 description 1
- 238000003118 sandwich ELISA Methods 0.000 description 1
- 230000000391 smoking effect Effects 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 230000002889 sympathetic effect Effects 0.000 description 1
- 230000005062 synaptic transmission Effects 0.000 description 1
- 230000035924 thermogenesis Effects 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 238000001262 western blot Methods 0.000 description 1
Classifications
-
- 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
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/574—Immunoassay; Biospecific binding assay; Materials therefor for cancer
- G01N33/57407—Specifically defined cancers
- G01N33/57415—Specifically defined cancers of breast
-
- 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
- C12Q1/6844—Nucleic acid amplification reactions
- C12Q1/6851—Quantitative amplification
-
- 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
- C12Q2600/118—Prognosis of disease development
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Immunology (AREA)
- Organic Chemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Molecular Biology (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Analytical Chemistry (AREA)
- Physics & Mathematics (AREA)
- Pathology (AREA)
- Microbiology (AREA)
- Genetics & Genomics (AREA)
- Biotechnology (AREA)
- General Health & Medical Sciences (AREA)
- Biochemistry (AREA)
- Urology & Nephrology (AREA)
- Hematology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Oncology (AREA)
- Hospice & Palliative Care (AREA)
- Biophysics (AREA)
- General Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Cell Biology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Physics & Mathematics (AREA)
- Medicinal Chemistry (AREA)
- Food Science & Technology (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
Abstract
The invention discloses a diagnosis and prognosis marker for breast cancer brain metastasis. In a first aspect, the invention provides the use of a reagent for quantitatively detecting markers including ADRA2A, ADRB3, HTR7 and CHRNA3 in the preparation of a kit for diagnosis of breast cancer brain metastasis and prognosis of breast cancer brain metastasis. The application according to the embodiment of the invention has at least the following beneficial effects: markers comprising the four genes (or expressed proteins thereof) are strongly correlated with recurrence of breast cancer brain metastasis, and therefore, whether a subject has developed breast cancer brain metastasis or a prognosis thereof can be effectively determined by quantitatively detecting the above markers.
Description
Technical Field
The application relates to the technical field of breast cancer diagnosis and treatment, in particular to a diagnosis and prognosis marker for breast cancer brain metastasis.
Background
Breast cancer is a common malignant tumor, along with the continuous development of technology, the treatment means of the breast cancer are gradually enriched, the survival time and quality of patients are obviously improved, but the local recurrence and the remote metastasis rate are still higher, and the metastasis sites of the breast cancer generally comprise bones, livers, lungs, brains, pleura, lymph and the like. Among them, the tendency of brain metastasis is high. For brain metastasis in breast cancer patients, a specific therapeutic guideline is lacking, and conventional therapeutic means take local treatment as a first choice. However, even if treatment means such as radiotherapy and surgery are performed, the metastatic lesions are easy to relapse, and the nerve function is rapidly affected, so that death is caused. In view of the high risk of brain metastases from breast cancer, early and effective assessment of patients helps to predict prognosis and guide treatment of individuals. However, the markers currently used for breast cancer metastasis risk assessment are mostly single genes. Therefore, there is a need to find related markers of breast cancer brain metastasis that have combined diagnostic value.
Disclosure of Invention
The present application aims to solve at least one of the technical problems existing in the prior art. Therefore, the application provides the marker of the breast cancer brain metastasis with good combined diagnosis value, and the reagent for quantitatively detecting the marker can be used for diagnosis or prognosis judgment of the breast cancer brain metastasis.
In a first aspect of the present application, there is provided the use of a reagent for quantitative detection of markers including ADRA2A, ADRB3, HTR7 and chra 3 in the manufacture of a kit for diagnosis of breast cancer brain metastasis, prognosis of breast cancer brain metastasis.
According to the application of the embodiment of the application, at least the following beneficial effects are achieved:
markers comprising the four genes (or expressed proteins thereof) are strongly correlated with recurrence of breast cancer brain metastasis, and therefore, whether a subject has developed breast cancer brain metastasis or a prognosis thereof can be effectively determined by quantitatively detecting the above markers.
Among them, ADRA2A (Adrenoceptor Alpha A, gene ID: 150) is an adrenergic receptor alpha2A gene, and the protein encoded by the gene is one of alpha-2-adrenergic receptors. The alpha-2-adrenergic receptor is a member of the superfamily of G protein-coupled receptors and inhibits adenylate cyclase, including 3 highly homologous subtypes: alpha2A (i.e., ADRA 2A), alpha2B, and alpha2C. They are involved in regulating the release of neurotransmitter molecules from adrenergic neurons in the sympathetic and central nervous systems. The sympathetic nervous system regulates cardiovascular function by activating adrenergic receptors in the heart, blood vessels and kidneys. Mouse studies have shown that alpha2A and alpha2C receptor subtypes are required for the release of presynaptic transmitters from the cardiac sympathetic nervous system and central noradrenergic neurons. There is no clear evidence at present for a clear association between alpha-2 adrenergic receptors and diseases.
ADRB3 (Adrenoceptor Beta, gene ID: 155) is the adrenergic receptor beta 3 gene. The protein encoded by this gene belongs to the family of beta adrenergic receptors, which mediate catecholamine-induced adenylate cyclase activation by the action of the G protein. The receptor is mainly located in adipose tissue and is involved in regulation of lipolysis and thermogenesis.
HTR7 (5-Hydroxytryptamine Receptor 7, gene ID: 3363) is a 5-hydroxytryptamine (serotonin) receptor 7 gene, and the serotonin receptor encoded by this gene belongs to the superfamily of G protein-coupled receptors, which is currently known as a candidate site involved in autism and other neuropsychiatric diseases.
Chra 3 (Cholinergic Receptor Nicotinic Alpha 3Subunit,Gene ID:1136) is a cholinergic receptor nicotinic α3subunit gene encoding a protein that is a member of the nicotinic acetylcholine receptor protein family. Members of this family of proteins are pentameric complexes formed by two alpha and one beta, one gamma and one delta subunits. And the gene encodes one of the alpha subunits, containing characteristic adjacent cysteine residues. The encoded protein is a ligand-gated ion channel, likely to play a role in neurotransmission. Only the polymorphism of this gene has been shown to be associated with increased smoking risk and increased susceptibility to lung cancer.
In some embodiments of the present application, the marker further comprises at least one of HTR3C, CHRNB 1.
HTR3C (5-Hydroxytryptamine Receptor C, gene ID: 3363) is a 5-hydroxytryptamine (serotonin) receptor 3C gene encoding subunit C of the 5-hydroxytryptamine (serotonin) type 3 receptor, a biological hormone, which acts as a neurotransmitter, hormone and mitogen. Such receptors, upon activation, cause a rapid depolarizing response in neurons.
CHRNB1 (Cholinergic Receptor Nicotinic Beta 1Subunit,Gene ID:1140) is a cholinergic receptor nicotinic β1subunit gene encoding a protein that is a member of the nicotinic acetylcholine receptor protein family. The protein is a pentameric complex formed from two alpha and one beta, one gamma and one delta subunits. The gene encodes a beta subunit therein.
In some embodiments of the present application, the agent quantitatively detects the marker at the gene level or protein level. The quantitative detection of nucleic acid at the gene level is carried out by methods including, but not limited to, polymerase Chain Reaction (PCR), isothermal amplification reaction (e.g., loop-mediated isothermal amplification LAMP, recombinase polymerase amplification RPA, etc.), probe hybridization technique, RNA blotting, etc. The quantitative detection of HTR6 proteins at the protein level is performed by methods including, but not limited to, enzyme-linked immunosorbent assay (ELISA), radioimmunoassay (IRA), immunohistochemical staining, western blot, electrophoresis, liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS), and the like.
In some embodiments of the present application, the reagent for quantitatively detecting the marker at the gene level is selected from the group consisting of a primer, a probe, and a gene chip. Wherein, the primer refers to a primer capable of specifically amplifying the marker gene, the probe refers to a probe capable of specifically recognizing the marker gene or the gene transcript, and the gene chip refers to a composite structure formed by immobilizing the array of the aforementioned probe on a substrate material (specifically including but not limited to a polymer such as nylon membrane, nitrocellulose membrane, glass, etc.).
In some embodiments of the present application, the reagent that quantitatively detects the marker at the protein level is an antibody. The antibody is an antibody capable of specifically recognizing the marker protein, and specifically includes at least one of a monoclonal antibody and a polyclonal antibody.
In a second aspect of the present application, there is provided a kit for diagnosis or prognosis of brain metastasis of breast cancer, the kit comprising reagents for quantitatively detecting markers including ADRA2A, ADRB3, HTR7 and chra 3.
In some embodiments of the present application, the marker further comprises at least one of HTR3C, CHRNB 1.
In some embodiments of the present application, the reagent is selected from the group consisting of primers, probes, gene chips, and antibodies. The primer means a primer capable of specifically amplifying the marker gene, the probe means a probe capable of specifically recognizing the marker gene or a transcript of the gene, the gene chip means a composite structure formed by immobilizing an array of the aforementioned probe on a substrate (specifically including but not limited to a polymer such as nylon membrane, nitrocellulose membrane, glass, etc.), and the antibody means an antibody capable of specifically recognizing the marker protein, specifically including at least one of a monoclonal antibody and a polyclonal antibody.
In some embodiments of the present application, when reagents detect the aforementioned markers at the gene level, the reagents may include, in addition to primers or probes, nucleic acid extraction reagents (including but not limited to nucleic acid extracts), PCR reaction reagents (including but not limited to dntps, taq enzymes, buffers), isothermal amplification reaction reagents (including but not limited to recombinases, single-stranded binding proteins, and strand displacement DNA polymerases); when the reagent detects the aforementioned markers at the protein level, the reagent may include an enzyme-linked immunoreactive reagent (including but not limited to a secondary enzyme-labeled antibody, a chromogenic solution) or other immunoreagent in addition to an antibody specifically recognizing the marker protein.
In some embodiments of the present application, the kit is an ELISA kit, such as a double antibody sandwich ELISA kit, a competition ELISA kit, or the like.
In some embodiments of the present application, reagents in the kit are immobilized on a test strip, and an immune colloidal gold test strip or other similar detection material is prepared, thereby improving the efficiency of on-site immediate detection.
Additional aspects and advantages of the application will be set forth in part in the description which follows, and in part will be obvious from the description, or may be learned by practice of the application.
Drawings
FIG. 1 is a heat map of differentially expressed genes in different risk groups for brain metastasis of breast cancer in example 1 of the present application.
FIG. 2 shows the expression of differentially expressed genes in different risk groups for brain metastasis in breast cancer in example 1 of the present application.
FIG. 3 is a survival curve between four gene expression levels and recurrence-free survival in different risk groups for brain metastasis of breast cancer in example 1 of the present application.
Fig. 4 is a survival curve between six gene expression levels and recurrence-free survival in different risk groups for brain metastases of breast cancer in example 1 of the application.
Fig. 5 is a time dependent ROC curve of four gene expression levels in different risk groups for brain metastasis of breast cancer in example 1 of the present application.
Fig. 6 is a time dependent ROC curve of six gene expression levels in different risk groups for brain metastasis of breast cancer in example 1 of the present application.
Detailed Description
The conception and technical effects produced by the present application will be clearly and completely described below in connection with the embodiments to fully understand the objects, features and effects of the present application. It is apparent that the described embodiments are only some embodiments of the present application, but not all embodiments, and that other embodiments obtained by those skilled in the art without inventive effort based on the embodiments of the present application are within the scope of the present application.
The following detailed description of embodiments of the present application is exemplary and is provided merely for purposes of explanation and not to be construed as limiting the application.
In the description of the present application, the meaning of a number is one or more, the meaning of a number is two or more, and greater than, less than, exceeding, etc. are understood to exclude the present number, and the meaning of a number above, below, within, etc. are understood to include the present number. The description of the first and second is for the purpose of distinguishing between technical features only and should not be construed as indicating or implying relative importance or implicitly indicating the number of technical features indicated or implicitly indicating the precedence of the technical features indicated.
In the description of the present application, a description with reference to the terms "one embodiment," "some embodiments," "illustrative embodiments," "examples," "specific examples," or "some examples," etc., means that a particular feature, structure, material, or characteristic described in connection with the embodiment or example is included in at least one embodiment or example of the present application. In this specification, schematic representations of the above terms do not necessarily refer to the same embodiments or examples. Furthermore, the particular features, structures, materials, or characteristics described may be combined in any suitable manner in any one or more embodiments or examples.
Example 1
The gene expression chip data (n=3951) of breast cancer patients in the Kaplan-Meier Plotter database were searched, and the correlation between 44 neurotransmitter receptor gene expression and breast cancer recurrence was analyzed, and 34 neurotransmitter receptor gene expression was found to be strongly correlated with breast cancer recurrence. Next, 34 receptors were analyzed for their relevance to breast cancer brain metastasis and recurrence by the SurvExpress program (http:// bioinformation. Mty. Itesm. Mx/SurvExpress), and six genes, CHRNB1, ADRA2A, ADRB3, HTR7, HTR3C, CHRNA, were found to combine to determine breast cancer brain metastasis and recurrence risk. The heat map of the differentially expressed genes is shown in FIG. 1, wherein the left side of the RISK band represents the low-RISK group and the right side represents the high-RISK group; the light grey in the Conser band indicates that 15 out of 188 individuals had data deleted due to insufficiency; time represents the survival Time of the individual. The differential expression of the different genes is shown in fig. 2, wherein the left data of each gene is a low risk group, and the right data is a high risk group. As can be seen in combination with fig. 1 and 2, there is a significant differential expression of the four genes HTR7, ADRA2A, CHRNA, ADRB3 in the high and low risk groups of brain metastases of breast cancer (p-values of 3.6x10, respectively -10 、5.53×10 -15 、5.25×10 -3 、4.26×10 -9 ) Whereas the differential expression of HTR3C, CHRNB1 in both groups was not significant (p values 0.439 and 0.489, respectively).
Further analysis of the previously retrieved data by the SurvExpress program verifies the relationship between the expression levels of the four genes HTR7, ADRA2A, CHRNA, ADRB3 combinations and the expression levels of the six genes HTR7, ADRA2A, CHRNA, ADRB3, HTR3C, CHRNB1 combinations for recurrence-free survival of breast cancer brain metastasis patients, as shown in fig. 3 and 4. Wherein, FIG. 3 is the result of four-gene combination, FIG. 4 is the result of six-gene combination, the lower curve in FIG. 3 and FIG. 4 represents the high risk group, and the upper curve represents the low risk group. HR (Hazard ratio) =3.98, p= 0.01884 in fig. 3; hr=10.93, p= 0.001927 in fig. 4. It can be seen that the relapse free survival time is significantly lower in the high risk group than in the low risk group. The marker formed by the four-gene combination and the six-gene combination has strong correlation with the recurrence risk of the breast cancer brain metastasis, but the six-gene combination is obviously more accurate for distinguishing the high risk group and the low risk group of the recurrence of the patient, and has higher diagnosis and prognosis values.
Time-dependent ROC curves at different time-cut points were plotted by the SurvExpress program using the above data in NNE (Nearest Neighbor Estimation) method as shown in fig. 5 and 6, respectively. Wherein FIG. 5 is a time-dependent ROC curve of four-gene combination and FIG. 6 is a time-dependent ROC curve of six-gene combination. As can be seen from the graph, the AUC values of the lower areas of the two genes in the time ranges from 10 months to 100 months (t=10, 20, 30, 40, 50, 60, 70, 80, 90, 100) are both above 0.7, and meanwhile, the AUC values of the six genes combined under the same time condition are higher, which indicates that the prediction performance of the six-gene-based prognosis model is better. Where t=10 in fig. 6, the AUC value can reach 0.925. Therefore, the four-gene or six-gene combination provided by the embodiment of the application is used as a marker to predict the risk of breast cancer brain metastasis and the accuracy of prognosis is higher.
Example 2
The expression levels of the six genes in example 1 were examined from samples of breast cancer tissue from patients who were pathologically diagnosed with breast cancer, confirmed with brain metastasis by imaging, and excluded from the cases of hospital visit, from the group consisting of male breast cancer, from the group consisting of primary tumors at other sites, from the group consisting of other serious organic lesions, and from patients who received radiotherapy or chemotherapy, and were measured as data sets according to 7:3 to a training set and a test set randomly, performing LASSO regression analysis to obtain a linear regression model of risk scores, dividing patients into a high risk group and a low risk group according to a risk score set threshold of the model, verifying the discrimination capability of the model by adopting a ROC curve, and adjusting the model to finally obtain a risk score model N=w1×HTR7+w2×ADR2A+w3×CHR3+w4×ADR3+w5×HTR3C+w6×CHRNB1 and a corresponding risk score threshold. w1 to w6 are parameter vector values corresponding to each gene, and N is a risk score. The expression levels of the six genes of the subject are detected by using the gene chip, and the result is substituted into the model, and if N is higher than a threshold value, the brain metastasis is more likely to occur.
The present application has been described in detail with reference to the embodiments, but the present application is not limited to the embodiments described above, and various changes can be made within the knowledge of one of ordinary skill in the art without departing from the spirit of the present application. Furthermore, embodiments of the present application and features of the embodiments may be combined with each other without conflict.
Claims (5)
1. Use of a reagent for quantitatively detecting markers including ADRA2A, ADRB3, HTR7 and chra 3 in the preparation of a kit for prognosis of brain metastasis of breast cancer.
2. The use of claim 1, wherein the marker further comprises at least one of HTR3C, CHRNB 1.
3. The use according to claim 1, wherein the reagent quantitatively detects the marker at the gene level or protein level.
4. The use according to claim 3, wherein said reagent for quantitatively detecting said marker at the gene level is selected from the group consisting of primers, probes and gene chips.
5. The use according to claim 3, wherein the reagent for quantitatively detecting the marker at the protein level is an antibody.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202111191448.2A CN113866415B (en) | 2021-10-13 | 2021-10-13 | Diagnostic and prognostic markers for breast cancer brain metastasis |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202111191448.2A CN113866415B (en) | 2021-10-13 | 2021-10-13 | Diagnostic and prognostic markers for breast cancer brain metastasis |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN113866415A CN113866415A (en) | 2021-12-31 |
| CN113866415B true CN113866415B (en) | 2024-02-06 |
Family
ID=78998835
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202111191448.2A Active CN113866415B (en) | 2021-10-13 | 2021-10-13 | Diagnostic and prognostic markers for breast cancer brain metastasis |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN113866415B (en) |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108348528A (en) * | 2015-09-17 | 2018-07-31 | 科达生物治疗公司 | Treat the composition and method of neurological disorder |
| CN108588226A (en) * | 2018-06-22 | 2018-09-28 | 南阳师范学院 | Detect the miRNA combination of breast cancer patients with brain transfer and the kit containing the combination |
| US11034751B1 (en) * | 2018-01-30 | 2021-06-15 | Flagship Pioneering Innovations V, Inc. | Methods and compositions for treating cancer using serotonin receptor inhibitors |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20140322243A1 (en) * | 2013-04-26 | 2014-10-30 | The Translational Genomics Research Institute | Methods of detecting breast cancer brain metastasis with genomic and epigenomic biomarkers |
| WO2018232195A1 (en) * | 2017-06-14 | 2018-12-20 | The Broad Institute, Inc. | Compositions and methods targeting complement component 3 for inhibiting tumor growth |
-
2021
- 2021-10-13 CN CN202111191448.2A patent/CN113866415B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108348528A (en) * | 2015-09-17 | 2018-07-31 | 科达生物治疗公司 | Treat the composition and method of neurological disorder |
| US11034751B1 (en) * | 2018-01-30 | 2021-06-15 | Flagship Pioneering Innovations V, Inc. | Methods and compositions for treating cancer using serotonin receptor inhibitors |
| CN108588226A (en) * | 2018-06-22 | 2018-09-28 | 南阳师范学院 | Detect the miRNA combination of breast cancer patients with brain transfer and the kit containing the combination |
Non-Patent Citations (4)
| Title |
|---|
| Breast CancerWith Brain Metastases: Clinicopathologic Features, Survival, and Paired Biomarker Analysis;QI SHEN等;《The Oncologist》;第20卷;第466–473页 * |
| Identification of potential genes related to breast cancer brain metastasis in breast cancer patients;Lijian Zhang等;《Bioscience Reports 》;第41卷;第BSR20211615:1-15页 * |
| 基于生物信息学对乳腺癌脑转移生物标志物的筛选与鉴定;邵明涛 等;《中国当代医药》;第28卷(第22期);第8-15页 * |
| 脑转移癌特异性标志物表达及其意义;王军臣 等;《中国癌症杂志》;第13卷(第5期);第453-455页 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN113866415A (en) | 2021-12-31 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| TWI661199B (en) | Urine markers for detection of bladder cancer | |
| JP5486718B2 (en) | Gene expression markers for prognosis of colorectal cancer | |
| KR101566368B1 (en) | Urine gene expression ratios for detection of cancer | |
| KR101032607B1 (en) | Proteinic markers for diagnosing hepatocellular carcinoma | |
| US20100190656A1 (en) | Breast Cancer Specific Markers and Methods of Use | |
| US20140206545A1 (en) | Gene expression markers for prediction of patient response to chemotherapy | |
| CN105648058A (en) | Marker for prognosis of liver cancer | |
| JP2020513574A (en) | Composition for diagnosing disease | |
| CN113866415B (en) | Diagnostic and prognostic markers for breast cancer brain metastasis | |
| KR101657051B1 (en) | Marker composition for diagnosis of chronic obstructive pulmonary disease | |
| CN110331207A (en) | Adenocarcinoma of lung biomarker and related application | |
| JP2021503289A (en) | New CIP2A variant and its use | |
| KR20170072685A (en) | A method for classification of subtype of triple-negative breast cancer | |
| JP2014183839A (en) | Diagnostic kit for diagnosis of pancreatic carcinoma in mammals, inspection method using the same and diagnostic marker | |
| CN114350799A (en) | Application of HTR2C in prognosis of low-grade glioma | |
| CN113943803A (en) | Application of HTR6 in diagnosis and prognosis of breast cancer | |
| EP3336547A1 (en) | Novel human bladder cancer biomarkers and their diagnostic use | |
| US10227656B2 (en) | Diagnostic/prognostic marker and therapeutic target for cancer | |
| KR102259708B1 (en) | Novel biomarker for predicting drug-responsibility to colon cancer | |
| KR102259695B1 (en) | Novel biomarker for predicting drug-responsibility to colon cancer | |
| KR102175265B1 (en) | Biomarker composition comprising TXNDC7 for diagnosis or predicting prognosis of hepatocellular carcinoma | |
| CN114807371A (en) | Application of reagent for detecting HTR6 in sample in preparation of prognosis product of low-grade glioma | |
| KR20210113140A (en) | Composition And Kit For Diagnosing Prognosis Of Kidney Cancer According To Tumor Type | |
| CN114317749A (en) | Application of HTR1A in prognosis of low-grade glioma | |
| CN117385034A (en) | Application of marker combination in preparation of product for predicting curative effect of prognosis treatment of liver cancer patient |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |