CN106018813A - Kit for detecting specificity of lip cancer - Google Patents

Kit for detecting specificity of lip cancer Download PDF

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Publication number
CN106018813A
CN106018813A CN201610624264.3A CN201610624264A CN106018813A CN 106018813 A CN106018813 A CN 106018813A CN 201610624264 A CN201610624264 A CN 201610624264A CN 106018813 A CN106018813 A CN 106018813A
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crisp1
aptamer
lip cancer
kit
dna
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陈博
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Individual
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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
    • 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
    • G01N33/57484—Immunoassay; Biospecific binding assay; Materials therefor for cancer involving compounds serving as markers for tumor, cancer, neoplasia, e.g. cellular determinants, receptors, heat shock/stress proteins, A-protein, oligosaccharides, metabolites
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C12N15/115—Aptamers, i.e. nucleic acids binding a target molecule specifically and with high affinity without hybridising therewith ; Nucleic acids binding to non-nucleic acids, e.g. aptamers
    • 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
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/10—Type of nucleic acid
    • C12N2310/16—Aptamers
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
    • G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
    • G01N2333/46—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans from vertebrates
    • G01N2333/47—Assays involving proteins of known structure or function as defined in the subgroups
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
    • G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
    • G01N2333/46—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans from vertebrates
    • G01N2333/47—Assays involving proteins of known structure or function as defined in the subgroups
    • G01N2333/4701—Details
    • G01N2333/4746—Cancer-associated SCM-recognition factor, CRISPP
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2800/00—Detection or diagnosis of diseases
    • G01N2800/18—Dental and oral disorders

Abstract

The invention discloses a kit for detecting specificity of lip cancer. An aptamer provided by the invention has good compatibility with human cysteinase-rich secretory proteins 1. By using the aptamer, the cysteinase-rich secretary proteins 1 in saliva can be captured, and the lip cancer is detected by virtue of the variation of the content of the cysteinase-rich secretary proteins 1. The cysteinase-rich secretary proteins 1 are prepared into a corresponding kit for screening the lip cancer. The kit has the advantages of high sensitivity and low cost.

Description

A kind of test kit of lip cancer specific detection
Technical field
The present invention relates to a kind of test kit for detecting lip cancer and detection method thereof.
Background technology
Lip cancer refers to that the malignant tumor betiding upper and lower lip is one of oral cavity common cancer, at oral cancer In account for and stand position, account for the 0.1%～0.5% of whole body malignant tumor, account for the 7.1%～15.0% of malignant tumor of mouth, American-European countries lip cancer patient is more, accounts for the 20%～30% of oral cancer.Typically lower lip is easier than upper lip gets involved, about 90%～95% occurs in vermilion border of lower lip portion, and is common at outer the 1/3 of W lower lip.Male patient is in the majority, The ratio of men and women is 7:1.Age occurred frequently is 50～70 years old.The lip cancer overwhelming majority is the shape cell carcinoma of differentiated, How occurring on the basis of the optimum pathological changes taking biology, its speed of growth is relatively slow, and prognosis is preferable, life in general 5 years The rate of depositing is on 70%W, and the cause of disease of primary disease may be stimulated by foreign body for a long time with local, and strong ultraviolet irradiates Relevant.Lip epithelium keratinization, white macula, skilful expense, granuloma and breach etc. are not healed for a long time, also may result in canceration.
Known in the art, saliva is that 10-40ng can be diagnosed as lip rich in hemiamic acid secretory protein 1 concentration Cancer.Therefore, the concentration of detection hemiamic acid secretory protein 1 becomes particularly important.
Aptamer (Aptamer, also known as aptamers, aptamer) is can high-affinity, the combination of high specific Certain biological leather El target strand widow's nucleic acid molecules (ssDNA or ssRNA).Aptamer is rich by index Collection Fas lignand system evolution technology (Systemat1c Evolut1on of L1gands by Exponent1al Enr1chment, SELEX) from the DNA/RNA library of synthetic screening obtain can high degree of specificity knot Close the single stranded DNA/RNA of target molecules.Reported the target of aptamer include metal ion, organic molecule, Polypeptide, protein, cell even tissue etc..The molecular recognition function of aptamer is similar with antibody, have with The target identification ability that antibody molecule is the most higher, but there is compared with antibody the most excellent characteristic, as Molecular weight is little, can manufacture, not easy in inactivation, non-immunogenicity, be readily synthesized with labelling, quickly penetrate Between tissue, good dynamic metabolism, different batches, product does not haves difference and has fine chemically stable Property, in fields such as biological detection, medical diagnosis on disease treatments, there is important application prospect.
Summary of the invention
It is an object of the invention to provide aptamer and the test kit thereof of a kind of specific bond CRISP1.
The aptamer that the present invention provides, is the single stranded DNA shown in sequence 1-15 of sequence table.
Described aptamer and CRISP1 albumen have preferable affinity.
Also described aptamer can be modified or transformed, obtain the derivant of described aptamer.
The derivant of described aptamer can be following any one:
A) described aptamer being deleted part or increases the nucleotide of partial complementarity, obtain fits with described nucleic acid Body has the derivant of the aptamer of identical function；
B) described aptamer carrying out nucleotide replacement or part is modified, obtain has with described aptamer The derivant of the aptamer of identical function；
C) transforming the skeleton of described aptamer as phosphorothioate backbone, obtain has with described aptamer There is the derivant of the aptamer of identical function；
D) aptamer is transform peptide nucleic acid(PNA) as, obtain with described aptamer have identical function nucleic acid fit The derivant of body；
E) after described aptamer being connected upper fluorescence, radioactivity and therapeutic substance, that obtain with described nucleic acid The derivant of the fit aptamer with identical function.
Described aptamer can be used for the test kit of preparation detection CRISP1.
Utilize the aptamer of the present invention, in can capturing in saliva in CRISP1, thus be used for being correlated with Oral cancer examination.Utilize the aptamer of the present invention, have highly sensitive, low cost, easily preparation, easily preservation Advantage.The present invention has the highest using value.
Detailed description of the invention
Below example facilitates a better understanding of the present invention, but does not limit the present invention.In following embodiment Experimental technique, if no special instructions, is conventional method.
Embodiment 1, the acquisition of CRISP1 albumen
By the eukaryotic expression mode by this area routine of the CRISP1 gene shown in Genbank:EAX04350 Express, it is thus achieved that corresponding desired polypeptides albumen.
The screening of embodiment 2 aptamer and preparation
Two ends comprise about 20 nucleotide, centre includes that the random nucleic acid library of 41 nucleotide is as follows in design:
5‘-TGGCACCTACGATCTAAGGCA(N41)GGACTACCAATGCAACGTCAC-3’；N41 represents 41 random nucleotides.
Being double-stranded DNA by single-stranded DNA banks amplification, product is through 2% agarose gel electrophoresis and cuts glue recovery purification； With reclaim double-stranded DNA as template, in vitro transcription goes out single stranded RNA random library, and transcription product is pure through PAGE Change.The RNA molecule being combined with film is removed, then with 2ug through anti-sieve of nitrocellulose filter in 75 μ g RNA libraries CRISP1 albumen, hatches 30min for 37 DEG C, and reactant liquor filters through nitrocellulose filter, washs filter membrane；Then Filter membrane is shredded, be placed in elution buffer (6mol/L carbamide, 0.55mol/L ammonium acetate, l.5mmol/L EDTA, 0.15%SDS) in boil 5min, centrifugal, take supernatant, dehydrated alcohol precipitation RNA, and again dissolve In 20 μ 1DEPC water；With RNA for template RT-PCR amplifying doulbe-chain DNA, in vitro transcription goes out RNA literary composition Storehouse is screened for next round；Often in wheel screening process, RT-PCR obtains double-stranded DNA library, with this double-stranded DNA Going out RNA aptamer storehouse for template in vitro transcription, screening carries out 12 altogether and takes turns.15 aptamers, its sequence are obtained Row are respectively shown in SEQ ID NO:1-15.Particular sequence is as follows:
CRISP1-1:
TGGCACCTACGATCTAAGGCAATCCCATATATGTTCCACACACTCGCAACTTATCCGCTACA GGACTACCAATGCAACGTCAC
CRISP1-2:
TGGCACCTACGATCTAAGGCATTCCGCCATAAATAAGATTCACATCACGACATCGATCACAC GGACTACCAATGCAACGTCAC
CRISP1-3:
TGGCACCTACGATCTAAGGCACTTAATCAACATATCTCTTCTGTATTCTCTCCACGCATACA GGACTACCAATGCAACGTCAC
CRISP1-4:
TGGCACCTACGATCTAAGGCAACGTCTCCAATCCGCACTTATAATTATGTTCTTACCTAAGA GGACTACCAATGCAACGTCAC
CRISP1-5:
TGGCACCTACGATCTAAGGCACGCTCATCACCATCTCCTACCTATATACATCACCTTCGCCT GGACTACCAATGCAACGTCAC
CRISP1-6:
TGGCACCTACGATCTAAGGCACATATCATCCTCCATACACGACCAACCACTCCGTCTTCACT GGACTACCAATGCAACGTCAC
CRISP1-7:
TGGCACCTACGATCTAAGGCAAACAAACACTCTCGCACATTACCTTATTTATCAAGAATATA GGACTACCAATGCAACGTCAC
CRISP1-8:
TGGCACCTACGATCTAAGGCACCGCTTATCTACACTAAATACAATTTCCTCCTCACCCTCCA GGACTACCAATGCAACGTCAC
CRISP1-9:
TGGCACCTACGATCTAAGGCACACGCCTCCAATATCAACTTAATAATACACCACTAATTTCT GGACTACCAATGCAACGTCAC
CRISP1-10:
TGGCACCTACGATCTAAGGCACACACGCCACTTATACAACAATCCAACCGCCTACCACTACT GGACTACCAATGCAACGTCAC
CRISP1-11:
TGGCACCTACGATCTAAGGCATAGCATCACTACTCGCTATTTCCTATAATCCTAGCCTTATA GGACTACCAATGCAACGTCAC
CRISP1-12:
TGGCACCTACGATCTAAGGCACTAGAAACTCCAACACATACACACACAGACCCGCTCCATAA GGACTACCAATGCAACGTCAC
CRISP1-13:
TGGCACCTACGATCTAAGGCATCGCATAACGCTCCACAATATTAACATACTTCTCTTCTTAT GGACTACCAATGCAACGTCAC
CRISP1-14:
TGGCACCTACGATCTAAGGCATCATAATATTCGCTCACTCTAATCATACATTATCTTCTTGT GGACTACCAATGCAACGTCAC
CRISP1-15:
TGGCACCTACGATCTAAGGCAATAATATTCGCTCACTATAATCAACATTATCTTCTTGTTCT GGACTACCAATGCAACGTCAC
The performance measurement of embodiment 3 protein binding aptamer
Aptamer is taken respectively 2.0 μ g, digests lh with calf intestinal alkaline phosphatase (CIP) 37 DEG C, pure Change and reclaim dephosphorylized RNA；By T4 polynucleotide kinase labelling [γ-32P] ATP in dephosphorylized RNA molecule end.The radiolabeled aptamer of 10nmol respectively with the CRISP1 of variable concentrations (1-200nM) Hatching 30min for 37 DEG C, each group reactant liquor filters through nitrocellulose filter, washs filter membrane, is dried filter membrane, liquid Dodging calculating instrument and measure the exit dose of residual on filter membrane, same sample is parallel does twice mensuration.Calculate each aptamer Dissociation constant with destination protein.Result is as follows:
Title Dissociation constant Kd (unit nM)
CRISP1-1 9.9
CRISP1-2 9.7
CRISP1-3 9.8
CRISP1-4 9.6
CRISP1-5 9.4
CRISP1-6 9.3
CRISP1-7 9.4
CRISP1-8 9.6
CRISP1-9 9.0
CRISP1-10 9.7
CRISP1-11 9.6
CRISP1-12 9.7
CRISP1-13 9.0
CRISP1-14 8.9
CRISP1-15 8.8
PBS blank Without binding ability
Aptamer specificity analyses and stability analysis described in embodiment 4
It is respectively adopted human albumin, immune globulin, vibrio cholera VgrG3C albumen, escherichia coli Outer membrane protein A, COCH albumen, CRISP1 albumen, carry out specific detection with 15 aptamers, pass through Binding tests finds, these aptamers do not combine with these albumen, and only protects with CRISP1 protein binding Hold higher specificity.
By described aptamer, take 0.2ug, be respectively placed in the serum of room temperature, aqueous solution, place two weeks. Detected by RT-PCR, find its Stability Analysis of Structures of placement of three weeks, be not degraded.
The diagnosis of aptamer disease described in embodiment 5
Take the salivation thing of 9 lip cancer patients and 3 normal persons, use normal saline dilution, it is thus achieved that target Sample.
By 15 markd aptamers of coupling, secretions with 9 patients and 3 normal persons mixes respectively 30min, is separated by biotin, the content of quantitative analysis CRISP1 therein albumen, is found by analysis, In 9 oral cancer patients, the content of CRISP1 albumen dramatically increases, and has exceeded the threshold value of regulation.Reach lip The diagnostic criteria of cancer.As can be seen here, its diagnosis effect is preferable.
These are only the preferred embodiments of the present invention, be not limited to the present invention, for the skill of this area For art personnel, all any modification, equivalent substitution and improvement etc. done within the spirit and principles in the present invention, Should be included within the scope of the present invention.
Sequence table
＜ 110 ＞ Chen Bo
The test kit of ＜ 120 ＞ mono-species-specific diagnosis lip cancer
〈160〉15
〈210〉1
〈211〉 83
〈212〉DNA
＜ 213 ＞ artificial sequence
〈400〉CRISP1-1
TGGCACCTACGATCTAAGGCAATCCCATATATGTTCCACACACTCGCAACTTATCCGCTACA GGACTACCAATGCAACGTCAC
〈210〉2
〈211〉 83
〈212〉DNA
＜ 213 ＞ artificial sequence
〈400〉CRISP1-2
TGGCACCTACGATCTAAGGCATTCCGCCATAAATAAGATTCACATCACGACATCGATCACAC GGACTACCAATGCAACGTCAC
〈210〉3
〈211〉 83
〈212〉DNA
＜ 213 ＞ artificial sequence
〈400〉CRISP1-3
TGGCACCTACGATCTAAGGCACTTAATCAACATATCTCTTCTGTATTCTCTCCACGCATACA GGACTACCAATGCAACGTCAC
〈210〉4
〈211〉 83
〈212〉DNA
＜ 213 ＞ artificial sequence
〈400〉CRISP1-4
TGGCACCTACGATCTAAGGCAACGTCTCCAATCCGCACTTATAATTATGTTCTTACCTAAGA GGACTACCAATGCAACGTCAC
〈210〉5
〈211〉 83
〈212〉DNA
＜ 213 ＞ artificial sequence
〈400〉CRISP1-5
TGGCACCTACGATCTAAGGCACGCTCATCACCATCTCCTACCTATATACATCACCTTCGCCT GGACTACCAATGCAACGTCAC
〈210〉6
〈211〉 83
〈212〉DNA
＜ 213 ＞ artificial sequence
〈400〉CRISP1-6
TGGCACCTACGATCTAAGGCACATATCATCCTCCATACACGACCAACCACTCCGTCTTCACT GGACTACCAATGCAACGTCAC
〈210〉7
〈211〉 83
〈212〉DNA
＜ 213 ＞ artificial sequence
〈400〉CRISP1-7
TGGCACCTACGATCTAAGGCAAACAAACACTCTCGCACATTACCTTATTTATCAAGAATATA GGACTACCAATGCAACGTCAC
〈210〉8
〈211〉 83
〈212〉DNA
＜ 213 ＞ artificial sequence
〈400〉CRISP1-8
TGGCACCTACGATCTAAGGCACCGCTTATCTACACTAAATACAATTTCCTCCTCACCCTCCA GGACTACCAATGCAACGTCAC
〈210〉9
〈211〉 83
〈212〉DNA
＜ 213 ＞ artificial sequence
〈400〉CRISP1-9
TGGCACCTACGATCTAAGGCACACGCCTCCAATATCAACTTAATAATACACCACTAATTTCT GGACTACCAATGCAACGTCAC
〈210〉10
〈211〉 83
〈212〉DNA
＜ 213 ＞ artificial sequence
〈400〉CRISP1-10
TGGCACCTACGATCTAAGGCACACACGCCACTTATACAACAATCCAACCGCCTACCACTACT GGACTACCAATGCAACGTCAC
〈210〉11
〈211〉 83
〈212〉DNA
＜ 213 ＞ artificial sequence
〈400〉CRISP1-11
TGGCACCTACGATCTAAGGCATAGCATCACTACTCGCTATTTCCTATAATCCTAGCCTTATA GGACTACCAATGCAACGTCAC
〈210〉12
〈211〉 83
〈212〉DNA
＜ 213 ＞ artificial sequence
〈400〉CRISP1-12
TGGCACCTACGATCTAAGGCACTAGAAACTCCAACACATACACACACAGACCCGCTCCATAA GGACTACCAATGCAACGTCAC
〈210〉13
〈211〉 83
〈212〉DNA
＜ 213 ＞ artificial sequence
〈400〉CRISP1-13
TGGCACCTACGATCTAAGGCATCGCATAACGCTCCACAATATTAACATACTTCTCTTCTTAT GGACTACCAATGCAACGTCAC
〈210〉14
〈211〉 83
〈212〉DNA
＜ 213 ＞ artificial sequence
〈400〉CRISP1-14
TGGCACCTACGATCTAAGGCATCATAATATTCGCTCACTCTAATCATACATTATCTTCTTGT GGACTACCAATGCAACGTCAC
〈210〉15
〈211〉 83
〈212〉DNA
＜ 213 ＞ artificial sequence
〈400〉CRISP1-15
TGGCACCTACGATCTAAGGCAATAATATTCGCTCACTATAATCAACATTATCTTCTTGTTCT GGACTACCAATGCAACGTCAC

Claims (3)

1., for a test kit for lip cancer detection, it contains the aptamer that energy specificity is combined with CRISP1 protein-specific.
2. test kit as claimed in claim 1, it is characterised in that: the sequence of described aptamer is as described in SEQ ID No:13.
3. the method detecting lip cancer, it is characterised in that utilize the test kit described in any one of claim 1-2.
CN201610624264.3A 2015-11-15 2015-11-15 Kit for detecting specificity of lip cancer Pending CN106018813A (en)

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CN201610624046.XA Pending CN106018811A (en) 2015-11-15 2015-11-15 Kit for detecting specificity of lip cancer
CN201610624264.3A Pending CN106018813A (en) 2015-11-15 2015-11-15 Kit for detecting specificity of lip cancer
CN201610624182.9A Pending CN106053846A (en) 2015-11-15 2015-11-15 Lip cancer specificity detection kit
CN201610624169.3A Withdrawn CN106226533A (en) 2015-11-15 2015-11-15 A kind of test kit of lip cancer specific detection
CN201610623977.8A Pending CN106053843A (en) 2015-11-15 2015-11-15 Lip cancer specificity detection kit
CN201610624332.6A Withdrawn CN106226534A (en) 2015-11-15 2015-11-15 A kind of test kit of lip cancer specific detection
CN201610624011.6A Pending CN106018810A (en) 2015-11-15 2015-11-15 Kit for detecting specificity of lip cancer
CN201610624012.0A Pending CN106053845A (en) 2015-11-15 2015-11-15 Lip cancer specificity detection kit
CN201510775706.XA Expired - Fee Related CN105353126B (en) 2015-11-15 2015-11-15 A kind of test kit of lip cancer specific detection
CN201610623940.5A Pending CN106053842A (en) 2015-11-15 2015-11-15 Lip cancer specificity detection kit
CN201610624160.2A Withdrawn CN106226532A (en) 2015-11-15 2015-11-15 A kind of test kit of lip cancer specific detection
CN201610623980.XA Pending CN106018833A (en) 2015-11-15 2015-11-15 Kit for detecting specificity of lip cancer
CN201610624284.0A Pending CN106053847A (en) 2015-11-15 2015-11-15 Lip cancer specificity detection kit
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CN201610623977.8A Pending CN106053843A (en) 2015-11-15 2015-11-15 Lip cancer specificity detection kit
CN201610624332.6A Withdrawn CN106226534A (en) 2015-11-15 2015-11-15 A kind of test kit of lip cancer specific detection
CN201610624011.6A Pending CN106018810A (en) 2015-11-15 2015-11-15 Kit for detecting specificity of lip cancer
CN201610624012.0A Pending CN106053845A (en) 2015-11-15 2015-11-15 Lip cancer specificity detection kit
CN201510775706.XA Expired - Fee Related CN105353126B (en) 2015-11-15 2015-11-15 A kind of test kit of lip cancer specific detection
CN201610623940.5A Pending CN106053842A (en) 2015-11-15 2015-11-15 Lip cancer specificity detection kit
CN201610624160.2A Withdrawn CN106226532A (en) 2015-11-15 2015-11-15 A kind of test kit of lip cancer specific detection
CN201610623980.XA Pending CN106018833A (en) 2015-11-15 2015-11-15 Kit for detecting specificity of lip cancer
CN201610624284.0A Pending CN106053847A (en) 2015-11-15 2015-11-15 Lip cancer specificity detection kit
CN201610624258.8A Pending CN106018812A (en) 2015-11-15 2015-11-15 Kit for specific detection of lip cancer

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