CN110055332A - Marker relevant to thyroid cancer and its application - Google Patents
Marker relevant to thyroid cancer and its application Download PDFInfo
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Abstract
The invention discloses marker relevant to thyroid cancer and its application, the marker is OIT3.The application and a kind of product of Diagnosis of Thyroid Carcinoma that the present invention provides OIT3 in the product for preparing Diagnosis of Thyroid Carcinoma.The present invention discloses application of the OIT3 in the computation model of building prediction thyroid cancer.
Description
Technical field
The invention belongs to biomedicine field, it is related to marker relevant to thyroid cancer and its application, is specifically related to
Marker is OIT3.
Background technique
Thyroid cancer is a kind of a kind of malignant tumour originating from thyroid follicular cells or parafollicular cell.
Thyroid cancer is worldwide in rising trend.Common thyroid cancer is divided into four classes, is thyroid papillary carcinoma respectively
(Papillary Thyroid Carcinoma, PTC), follicular carcinoma of thyroid (follicular thyroid
Carcinoma, FTC), medullary carcinoma of thyroid gland (medullary thyroid carcinoma, MTC), anaplastic thyroid carcinoma
(anaplastic thyroid carcinoma, ATC).Thyroid papillary carcinoma is the most common thyroid cancer, accounts for thyroid gland
70% (Lin HW, Bhattacharyya N.Clinical behavoir of follicular variant of malignant tumour
of papillary thyroid carcinoma:presentation and survival[J].Laryngosocope,
2012,120 (4): 712-716.), 10 years survival rates of patient are greater than 90% (Ito Y, Miyauchi A.Prognostic
factors and therapeutic strategies for differentiated carcinomas of the
thyroid[J].Endocr J,2009,56(20):177-192.)；But still some PTC patient's prognosis is poor, this can
It can be related with the hypotype of PTC.In addition to most common classic thyroid papillary carcinoma (Classical Papillary
Thyroid Carcinoma, CPTC) outside, PTC still has 15 hypotypes.Although patient's number that the current country is diagnosed as PTC increases rapidly
Add, still, either clinician or pathologist still have deficiency to the understanding of PTC hypotype, mistaken diagnosis and treatment easily occur
Situations such as improper.
Folliculus hypotype (Follicular Variant of Papillary Thyroid Carcinoma, FVPTC) is
The most common hypotype in PTC, accounts for the 20%~30% of whole PTC；Its diagnostic criteria are as follows: 50% folliculus knot is had more than in lesion
Structure, without the nipple structure well broken up, have the typical nuclear characteristics of PTC (Nikiforov YE, Biddinger PW,
Thompson LDR.Diagnostic pathology and molecular Genetics of thyroid[M]
.Philadelphia:Lippincott Williams and Wilkins,2012:473-673.).FVPTC is examined in recent years
Disconnected rate obviously rises, and has caused clinical workers to its attention and has carried out many researchs but also still remained much not yet to solve
Certainly the problem of, if FVPTC preoperative diagnosis is more difficult, as the diagnostic method that thyroid malignancy clinical guidelines are recommended, i.e.,
FNA checks the problem lower there is also sensibility, and remain to be discovered efficient preoperative diagnosis method；Secondly, currently there is an urgent need to bright
The pathology and biological property of true FVPTC, the formulation of further guiding clinical treatment scheme.
Summary of the invention
In order to make up for the deficiencies of the prior art, the purpose of the present invention is to provide marker relevant to thyroid cancer and its
Application in diagnosis of thyroid cancer and treatment.
To achieve the goals above, the present invention adopts the following technical scheme:
The present invention provides application of the reagent of detection OIT3 in the product for preparing Diagnosis of Thyroid Carcinoma.
Further, the reagent is selected from oligonucleotide probe, the specific amplification OIT3 base of specific recognition OIT3 gene
The bonding agent of the albumen of the primer or specific binding OIT3 gene coding of cause.
Further, the primer sequence of the specific amplification OIT3 gene such as SEQ ID NO.1 and SEQ ID NO.2 institute
Show.
Further, the thyroid cancer is follicular thyroid papillary carcinoma.
The present invention provides a kind of product of Diagnosis of Thyroid Carcinoma, the product includes being able to detect OIT3 expression
Chip, kit or nucleic acid film item.
Further, the chip includes genetic chip, protein chip, and the genetic chip includes for detecting OIT3 gene
The oligonucleotide probe for OIT3 gene of transcriptional level, the protein chip include the specific binding agent of OIT3 albumen；
The kit includes gene detecting kit, protein detection kit, and the gene detecting kit includes for detecting
The reagent or chip of OIT3 gene transcription level, the protein detection kit include for detecting OIT3 protein expression level
Reagent or chip.
Further, the kit include by RT-PCR method, qRT-PCR method, biochip test method, southern blotting technique method,
The reagent of hybridization in situ, Western blot detection OIT3 gene or protein expression level.
Further, the reagent with qRT-PCR method detection OIT3 gene expression dose include such as SEQ ID NO.1 and
The primer sequence of specific amplification OIT3 gene shown in SEQ ID NO.2.
The present invention provides application of the OIT3 in the computation model of building prediction thyroid cancer.
The present invention provides application of the OIT3 in the pharmaceutical composition of preparation treatment thyroid cancer.
Further, described pharmaceutical composition includes the Functional Inhibitors of OIT3.
The advantages of the present invention:
Present invention firstly discovers that a kind of relevant molecular marker-OIT3 gene of occurrence and development to thyroid cancer, leads to
Cross the expression of OIT3 in detection subject's parathyroid tissue, it can be determined that whether subject suffers from thyroid cancer, to refer to
It leads clinician and provides prevention scheme or therapeutic scheme to subject；The diagnosis of disease is realized using molecular marked compound and is controlled
It treats, compares traditional means, there is higher specificity and sensitivity.
Detailed description of the invention
Fig. 1 shows the expression figure using QPCR detection OIT3 gene in human thyroid carcinoma.
Detailed description of the invention
The present invention is by extensive and in-depth research, using the method for high-flux sequence combination analysis of biological information, screening
The gene of differential expression is presented in thyroid cancer sample, and screened differential expression is verified by the further large sample of QPCR
Gene be applied to thyroid cancer in feasibility, exclude false positive, provide molecule for the diagnosis and targeted therapy of thyroid cancer
Means.By screening, present invention firstly discovers that expression of the OIT3 in thyroid cancer significantly raises.
OIT3 includes wild type, saltant type or its segment.The term covers overall length, unprocessed OIT3, and is originated from thin
Any type of OIT3 processed in born of the same parents.The term covers the natural generation variant of OIT3, and (such as splice variant or equipotential become
Body).The term covers such as OIT3 gene, the mRNA sequence (GenBank accession number NM_152635.3) of people OIT3 and people
The amino acid sequence (GenBank accession number NP_689848.1) of OIT3 and come from any other vertebrate origin, including feed
The OIT3DNA of newborn animal, such as Primate and rodent (such as mouse and rat), mRNA and amino acid sequence.As
A kind of preferred embodiment, in the present invention, OIT3 are the gene of people, gene I/D 170392.
Terms used herein " differential expression " indicates to mark with one or more present invention biologies identical in second of sample
The expression of will object compares, after measured the amount or level of mRNA, one or more biology marks of the invention in a sample
The difference of one or more splice variant expressions of the RNA of the will object and/or biomarker mRNA." differential expression
" it can also include compared with protein expression quantity in second of sample or sample group or level, to this in sample or sample group
The measurement of the protein of invention biomarker coding.Differential expression can it is as described herein and those skilled in the art understand that
Method determines.Given biomarker can in term " differential expression " or " variation of expression " expression and second of sample
Measurement expression compares, after measured the amount of RNA and/or the amount of protein, and expression can be measured by giving biomarker in sample
Horizontal increases or decreases.Term " differential expression " or " variation of expression " also may indicate that and life in second sample group
The expression that measures of object marker compares, and biomarker is given in sample group can measure the increase or drop of expression
It is low." differential expression " used herein can be with the expression of given biomarker relative to biomarker given in control
The ratio of Average expression level be measured, wherein ratio is not equal to 1.0.Differential expression can also be measured with p value.Work as use
When p value, when p value is less than 0.1, biomarker is accredited as the differential expression between the first and second groups.More preferable p value
Less than 0.05.Even more preferably p value is less than 0.01.Even more preferably from p value less than 0.005.Most preferably p value is less than 0.001.When being based on
When ratio determines differential expression, if the ratio of expression is more than or less than 1.0, RNA in the first and second of sample
Or protein is differential expression.For example, the ratio greater than 1.2,1.5,1.7,2,3,4,10,20, or the ratio less than 1
Rate, such as 0.8,0.6,0.4,0.2,0.1,0.05.In another embodiment of the present invention, if the first group is averaged
The ratio of expression and the Average expression level of the second group is more than or less than 1.0, then transcribed nucleic acid is originally differential expression.
For example, the ratio greater than 1.2,1.5,1.7,2,3,4,10,20, or the ratio less than 1, for example, 0.8,0.6,0.4,0.2,
0.1,0.05.In another embodiment of the present invention, if put down in expression and second colony in first sample
The ratio of equal expression is more than or less than 1.0, is greater than 1.2,1.5,1.7,2,3,4,10,20 or ratio for example including ratio
Less than 1, such as 0.8,0.6,0.4,0.2,0.1,0.05, then transcribed nucleic acid is originally differential expression.
" differential expression increase " or " up-regulation " indicates gene relative in contrast, and gene expression is (with rna expression or albumen
Matter expression measurement) display increase at least 10% or more, such as 20%, 30%, 40% or 50%, 60%, 70%, 80%,
90% or more or 1.1 times, 1.2 times, 1.4 times, 1.6 times, 1.8 times or more.
" differential expression reduction " or " downward " indicates gene relative in contrast, and gene expression is (with rna expression or albumen
Matter expression measurement) display reduce at least 10% or more, such as 20%, 30%, 40% or 50%, 60%, 70%, 80%,
90% or less than 1.0 times, 0.8 times, 0.6 times, 0.4 times, 0.2 times, 0.1 times or less gene.For example, up-regulation gene include with
The expression of the mRNA or protein that separate from normal individual are compared, from the sample of the individual separation characterized by with thyroid cancer
Middle mRNA or the increased gene of protein expression level.For example, down-regulated gene include compared with the sample separated from normal individual,
The gene that mRNA or protein expression level reduce from the sample of the individual separation characterized by with thyroid cancer.
It herein include the available method for detecting inherent gene expression as described herein in any this field." detection table
Up to " refer to the determining inherent RNA transcript of gene or the amount or presence of its expression product.Detect the inherent gene table of the disclosure
It reaches, i.e. the method for gene expression profile analysis is included method based on polynucleotides hybridization analysis, is sequenced based on polynucleotides
Method, ImmunohistochemistryMethods Methods and the method based on proteomics.These methods usually detect inherent gene as described herein
Expression product (such as mRNA).In preferred embodiments, using the method for based on PCR, such as reverse transcription PCR (RT-
), and such as microarray of the method based on array PCR." microarray " refer to can hybridised arrays element, e.g., for example, polynucleotides visit
Needle, the ordered arrangement in matrix.Term " probe ", which refers to, such as to be encoded by inherent gene with especially expected target biomolecule
Or molecule that nucleotide transcript or protein selectivity corresponding to inherent gene combine.Probe can be by those skilled in the art
Member's synthesis, or may come from suitable Biological preparation.Probe can specifically be designed to be marked.It can be with
The example of molecule as probe includes, but are not limited to RNA, DNA, albumen, antibody and organic molecule.
In the present invention, the oligonucleotide probe for OIT3 gene can be DNA, RNA, DNA-RNA chimera, PNA
Or other derivatives.There is no limit as long as complete specific hybrid and purpose nucleotide sequence specificity for the length of the probe
In conjunction with any length is ok.The length of the probe can be as short as 25,20,15,13 or 10 bases longs.Equally, the spy
The length of needle can be grown to 60,80,100,150,300 base-pairs or longer or even whole genes.Due to different probe lengths
There is different influences to hybridization efficiency, signal specificity, the length of the probe is typically at least 14 base-pairs, and longest is general
No more than 30 base-pairs, the length complementary with purpose nucleotide sequence are best with 15-25 base-pair.The probe itself is mutual
Complementary series is most preferably less than 4 base-pairs, in order to avoid influence hybridization efficiency.
The bonding agent such as receptor of protein OIT3 of the albumen of OIT3 gene coding is specifically bound in the present invention, is combined
The agglutinin of protein OIT3, the antibody for protein OIT3, the peptide antibody (peptidebody) for protein OIT3,
The agent of bispecific dual combination or bispecific antibody form.The specific example of specific binding agent be peptide, peptide mimics,
Aptamer, spiegelmer, darpin, ankyrin repeat protein, Kunitz type domain, antibody, single domain antibody and univalent antibody piece
Section.In a specific embodiment of the present invention, the specific binding agent is OIT3 specific antibody.
Heretofore described chip, kit or film item can be used for detecting multiple genes including OIT3 gene and
The expression of its expression product (for example, multiple genes relevant to thyroid cancer).Multiple markers of thyroid cancer are same
Shi Jinhang detection, is greatly improved the accuracy rate of diagnosis of thyroid cancer.
The present invention provides application of the OIT3 in the computation model of building prediction thyroid cancer, as those of skill in the art
Know, can be implemented in various ways and realize the step of marker levels and certain possibility or risk association are got up.
Preferably, the mathematically measurement concentration of composite marker object and one or more other markers, and by combined value and basic
Diagnosis problem associates.It can be combined the measurement of marker levels by any suitable prior art mathematical method.
Preferably, the mathematical algorithm applied in marker combination is a kind of logarithmic function.Preferably, using such mathematics
Algorithm or such logarithmic function the result is that single value.According to basic diagnosis problem, can easily by such value with it is for example a
Body associates about the risk of thyroid cancer or with the other intentional diagnostic uses for helping to assess thyroid cancer patients.With one
Kind preferred mode, such logarithmic function obtain as follows: individual segregation a) being entered group, such as normal person, has thyroid cancer
The individual of risk, the patient with thyroid cancer etc., b) significant difference between these groups is identified by univariate analysis
Marker, c) logarithmic regressions analysis to be to assess the independent difference values that can be used for assessing these difference groups of marker, and d) structure
It builds logarithmic function and carrys out composition independency difference value.In such analysis, marker is no longer independent, but represents one
Marker combination.
Logarithmic function for marker combination to be got up with disease association is preferably developed using by applied statistical method
With the algorithm of acquisition.For example, suitable statistical method is discriminant analysis (DA) (i.e. linear, secondary, regular DA), Kernel method
(i.e. SVM), nonparametric technique (i.e. k- nearest neighbor classifiers), PLS (partial least square), method (the i.e. logic based on tree
Recurrence, CART, random forest method, boosting/bagging method), generalized linear model (i.e. logarithm regression), the side based on principal component
Method (i.e. SIMCA), broad sense Additive Model, the method based on fuzzy logic, the method based on artificial neural network and genetic algorithms.Skillfully
Technical staff merges in the suitable statistical method of selection to assess marker group of the invention thus to obtain suitable mathematical algorithm
Aspect will not be problematic.In one embodiment, for obtaining the statistics side of mathematical algorithm used in assessment thyroid cancer
Method is selected from DA (i.e. linear, secondary, rule based judgment analysis), Kernel method (i.e. SVM), nonparametric technique (i.e. k- nearest-neighbors
Classifier), PLS (partial least square), method (i.e. logistic regression, CART, random forest method, boosting side based on tree
Method) or generalized linear model (i.e. logarithm regression).
The present invention provides application of the OIT3 in the pharmaceutical composition of preparation treatment thyroid cancer, described pharmaceutical compositions
Inhibitor including OIT3 functional expression.The inhibitor refers to any activity for reducing OIT3 albumen, reduces OIT3 base
Because or albumen stability, lower OIT3 albumen expression, reduce OIT3 albumen effective acting time or inhibit OIT3 gene
The substance of transcription and translation, these substances are used equally for the present invention, as the substance useful for downward OIT3, so as to be used for
Prevention or treatment thyroid cancer.Inhibitor includes nucleic acid inhibitor, protein inhibitor, proteolytic enzyme, albumen to example as mentioned
Binding molecule.Wherein nucleic acid inhibitor is selected from: using OIT3 or its transcript as target sequence and be able to suppress OIT3 gene expression or
The disturbing molecule of genetic transcription, comprising: shRNA (children purpura nephritis), siRNA (siRNA), dsRNA, Microrna, antisense
Nucleic acid, or can express or be formed the construction of the shRNA, siRNA, dsRNA, Microrna, antisense nucleic acid.Albumen knot
Close molecule to be selected from: the substance in conjunction with OIT3 protein-specific is such as able to suppress the antibody or ligand of OIT3 protein active.
The inhibitor of OIT3 can be given by liposome in the present invention, the effect of the liposome be by drug targeting in
Specific tissue, and increase the half-life period of drug.Liposome includes emulsifier, foaming agent, liquid fatty substance, Solid lipid, no
Dissolubility single layer, phospholipid dispersions, surfactant etc..Can also include in the liposome can in the cell of targeting by
Body molecule combines or other therapeutic or immunogenic composition.
Drug of the invention can also can be with master with the drug combination of other treatment thyroid cancer, other therapeutic compound
The active constituent (for example, inhibitor of OIT3) wanted is administered simultaneously, or even is administered simultaneously in same composition.It can also be with list
Only composition or the dosage form different from main active constituent individually give other therapeutic compounds.Main component
The Fractional of (such as OIT3 inhibitor) can be administered simultaneously with other therapeutic compounds, and other dosage can individually be given
Medicine.
Specific embodiment
The present invention is described in further detail with reference to the accompanying drawings and examples.Following embodiment is merely to illustrate this
It invents rather than limits the scope of the invention.The simple modifications that essence according to the present invention carries out the present invention belong to this hair
Bright claimed range.
Embodiment 1 screens gene marker relevant to thyroid cancer
1, sample collection
4 follicular Papillary Thyroid Carcinomas and cancer beside organism's sample are collected respectively, exclude other malignant tumours trouble
Person, the acquirement of above-mentioned all samples pass through the agreement of the committee, organizational ethics.
2, the preparation of RNA sample
Total tissue RNA is extracted using TRIZOL method
1) it is shredded with scissors tissue, 1ml Trizol is added, shakes 1min on oscillator；Room temperature 10min makes core egg
Lean type is decomposed completely.
2) 200 μ l chloroforms (chloroform) are added, cover tightly pipe lid, acutely shake 15s, room temperature stands 10min.
3) 4 DEG C, 11000rpm is centrifuged 15min.
4) water sample layer is transferred in a new centrifuge tube, 500 μ l isopropanols is added；After being mixed by inversion, room temperature is stood
10min。
5) 4 DEG C, 11000rpm is centrifuged 15min.
6) liquid is carefully siphoned away with rifle, stays and is deposited in tube bottom, the ethyl alcohol of 1ml 75% is added, shakes 5s on the oscillator,
Washing precipitating is primary.
7) 4 DEG C, 8000rpm is centrifuged 5min.
8) supernatant is carefully removed, drying precipitated 10min, suitable water dissolution precipitating 10min is added.
9) RNA concentration is detected, identifies the yield and purity of RNA.
3, construction cDNA library
Use the rRNA removed in total serum IgE with the Ribo-Zero kit of Epicentre；It will using metal ion
Complete RNA is broken into the small fragment of 200bp or so at random.
The building of cDNA library, concrete operations are carried out using the TruseqTM RNA sample Prep Kit of Illumina
It is detailed in specification.
4, it is sequenced
Qualified library to be detected, NaOH denaturation is added at single-stranded, the library after denaturation dilution is added in FlowCell, with
Connector hybridization on FlowCell, bridge-type PCR amplification is completed on cBot, is surveyed using Illumina X-Ten microarray dataset
Sequence.
5, high-throughput transcript profile sequencing data analysis
Bioinformatic analysis is carried out to sequencing result, is carried out using reads number of the DESeq packet in R software to gene
Analysis, sets screening criteria as P < 0.05.
6, result
High-flux sequence interpretation of result shows that expression quantity of the OIT3 gene in follicular Papillary Thyroid Carcinoma is aobvious
It writes and is higher than cancer beside organism.
The differential expression of 2 QPCR sequence verification OIT3 gene of embodiment
1, large sample QPCR verifying is carried out to OIT3 gene differential expression.According to the sample collection mode in embodiment 1 point
It Shou Ji not 30 cancerous tissue samples and cancer beside organism's sample.
2, RNA extraction step is the same as embodiment 1
3, real-time quantitative PCR detects
1) it reverse transcription: is operated using the reverse transcription reagent box (Takara code:DRR047A) of TAKARA company.
A. genomic DNA is removed
5 × gDNA Eraser B μ ffer, 2.0 μ l, gDNA Eraser 1.0 μ l, 1 μ g of total serum IgE are added in test tube,
Add Rnase Free ddH2O makes total volume to 10 μ l, 42 DEG C of heating 2min in water-bath.
B. reverse transcription reaction
It will2 4.0 μ l of Buffer,RT Enzyme Mix I 1.0 μ l, RT
1.0 μ l, RNase Free ddH of Primer Mix24.0 μ l of O, which is added in above-mentioned test tube, is mixed together totally 20 μ l, in water-bath
37 DEG C of 15min, 85 DEG C of 5s.
2) QPCR is expanded
A. design of primers
According to the gene order design primer of OIT3 and GADPH, specific primer sequence is as follows:
OIT3 gene:
Forward primer is 5 '-CTAAGAAGTGATGGCAAGAC-3 ' (SEQ ID NO.1)；
Reverse primer is 5 '-TCAGATCCAAGGCAAGAG-3 ' (SEQ ID NO.2).
GAPDH gene:
Forward primer is 5 '-AATCCCATCACCATCTTCCAG-3 ' (SEQ ID NO.3)；
Reverse primer is 5 '-GAGCCCCAGCCTTCTCCAT-3 ' (SEQ ID NO.4).
B.QPCR amplification is examined
WithPremix Ex TaqTMII (Takara Code:DRR081) kit configures PCR reaction system,
In Thermal CyclerPCR amplification is carried out on Real Time System amplification instrument, confirms Real after reaction
The amplification curve and solubility curve of Time PCR, Δ Δ CT method carry out relative quantification.
Configure 25 μ l reaction systems:
Premix Ex TaqTM II (2 ×) 12.5 μ l, it is positive (anti-) to go out to each 1 μ l of primer, 2 μ l of DNA profiling
8.5 μ l of bacterium distilled water.
Reaction condition: 95 DEG C of 30s, (95 DEG C of 5s, 60 DEG C of 30s) × 40
4, result
For QPCR result as shown in Figure 1, compared with cancer beside organism, OIT3 expresses significant up-regulation in human thyroid carcinoma, poor
It is different that there is statistical significance (P < 0.05), it is consistent with high-flux sequence result；Wherein expression up-regulation has 29, and OIT3 is prompted to exist
Application value with higher in the diagnosis of thyroid cancer.
The explanation of above-described embodiment is only intended to understand method and its core concept of the invention.It should be pointed out that for this
For the those of ordinary skill in field, without departing from the principle of the present invention, several improvement can also be carried out to the present invention
And modification, these improvement and modification will also be fallen into the protection scope of the claims in the present invention.
Sequence table
<110>the 9th 60 hospital, Chinese People's Liberation Army's joint logistics system army
<120>marker relevant to thyroid cancer and its application
<160> 4
<170> SIPOSequenceListing 1.0
<210> 1
<211> 20
<212> DNA
<213>artificial sequence (Artificial Sequence)
<400> 1
ctaagaagtg atggcaagac 20
<210> 2
<211> 18
<212> DNA
<213>artificial sequence (Artificial Sequence)
<400> 2
tcagatccaa ggcaagag 18
<210> 3
<211> 21
<212> DNA
<213>artificial sequence (Artificial Sequence)
<400> 3
aatcccatca ccatcttcca g 21
<210> 4
<211> 19
<212> DNA
<213>artificial sequence (Artificial Sequence)
<400> 4
gagccccagc cttctccat 19
Claims (10)
1. detecting application of the reagent of OIT3 in the product for preparing Diagnosis of Thyroid Carcinoma.
2. application according to claim 1, which is characterized in that the reagent is selected from the few core of specific recognition OIT3 gene
The bonding agent of the albumen of thuja acid probe, the primer of specific amplification OIT3 gene or specific binding OIT3 gene coding.
3. application according to claim 2, which is characterized in that the primer sequence of the specific amplification OIT3 gene is such as
Shown in SEQ ID NO.1 and SEQ ID NO.2.
4. application according to claim 1-3, which is characterized in that the thyroid cancer is follicular thyroid gland cream
Head cancer.
5. a kind of product of Diagnosis of Thyroid Carcinoma, which is characterized in that the product includes the core for being able to detect OIT3 expression
Piece, kit or nucleic acid film item.
6. product according to claim 5, which is characterized in that the chip includes genetic chip, protein chip, the base
Because chip includes the oligonucleotide probe for OIT3 gene for detecting OIT3 gene transcription level, the protein chip packet
Include the specific binding agent of OIT3 albumen；The kit includes gene detecting kit, protein detection kit, the gene
Detection kit includes the reagent or chip for detecting OIT3 gene transcription level, and the protein detection kit includes using
In the reagent or chip of detection OIT3 protein expression level.
7. product according to claim 6, which is characterized in that the kit includes passing through RT-PCR method, qRT-PCR
Method, biochip test method, southern blotting technique method, hybridization in situ, Western blot detection OIT3 gene or protein expression level
Reagent.
8. product according to claim 7, which is characterized in that described to detect OIT3 gene expression dose with qRT-PCR method
Reagent include the specific amplification OIT3 gene as shown in SEQ ID NO.1 and SEQ ID NO.2 primer sequence.
Application of the 9.OIT3 in the computation model of building prediction thyroid cancer.
Application of the 10.OIT3 in the pharmaceutical composition of preparation treatment thyroid cancer.
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| CN201910406301.7A CN110055332A (en) | 2019-05-16 | 2019-05-16 | Marker relevant to thyroid cancer and its application |
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| CN201910406301.7A CN110055332A (en) | 2019-05-16 | 2019-05-16 | Marker relevant to thyroid cancer and its application |
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| CN110184358A (en) * | 2019-06-25 | 2019-08-30 | 台州市立医院 | The OIT3 gene of thyroid cancer early diagnosis and its application |
| CN111424092A (en) * | 2020-04-22 | 2020-07-17 | 中国人民解放军联勤保障部队第九六0医院 | Detection gene and application thereof |
| CN114717320A (en) * | 2022-04-21 | 2022-07-08 | 中山大学附属第一医院 | Novel liver cancer tumor marker and application thereof |
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Application publication date: 20190726 |