CN110093423A - Purposes of the gene marker in adenocarcinoma of lung diagnosis and treatment - Google Patents

Purposes of the gene marker in adenocarcinoma of lung diagnosis and treatment Download PDF

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CN110093423A
CN110093423A CN201910438450.1A CN201910438450A CN110093423A CN 110093423 A CN110093423 A CN 110093423A CN 201910438450 A CN201910438450 A CN 201910438450A CN 110093423 A CN110093423 A CN 110093423A
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lung
linc02154
adenocarcinoma
gene
product
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徐红玉
张涛
苏晓妹
张伶
程朋
高辉
李东
李华
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Western Theater General Hospital of PLA
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Abstract

The invention discloses purposes of the gene marker in adenocarcinoma of lung diagnosis and treatment, the gene marker is lncRNA LINC02154, LINC02154 is in low expression in pulmonary adenocarcinoma, pass through expression of the detection LINC02154 in subject, it can be determined that whether subject suffers from adenocarcinoma of lung or suffer from the risk of adenocarcinoma of lung.

Description

Purposes of the gene marker in adenocarcinoma of lung diagnosis and treatment
Technical field
The invention belongs to biomedicine fields, are related to purposes of the gene marker in adenocarcinoma of lung diagnosis and treatment, are specifically related to Gene marker be LINC02154.
Background technique
Lung cancer is one of highest cancer of the global death rate, no matter its disease incidence of gender and the death rate are respectively positioned on first three (Siegel RL,Miller KD,Jemal A:Cancer statistics,2015.CA:a cancer journal for clinicians 2015,65(1):5-29.).Early discovery, early diagnosis, early treatment it is particularly significant in the diagnosis and treatment of lung cancer sufferer and Necessity, very likely there is transfer of the lung carcinoma cell to other each different organs in advanced lung cancer sufferer, so that suffering from lung cancer The major reason of person's life quality decline and poor prognosis.Although clinical constantly update pulmonary cancer diagnosis and treatment technology and method It regenerates, but the whole outcome after lung cancer therapy is still undesirable, the death rate still occupies first of various cancers, patient's 5 annual survival rates are still less than 15%.About 85% the above are non-small cell lung cancer in lung cancer patient, at this stage most effective treatment method It is early stage patient based on surgical operation therapy, middle and advanced stage patient is using chemicotherapy and the complex treatment of targeting immunization therapy. Regardless of whether the patient that can be performed the operation, overall survival is all undesirable, seriously affects and endangers human health and life.It is early to find, is early Diagnosis, early treatment and effective prediction prognosis are particularly significant in lung cancer diagnosis and treatment whole process.
Recently as the attention and further investigation lung cancer occurred with tumour growth mechanism, some important therapy targets Also it is gradually found, and the precisely trial and breakthrough of targeted therapies, these all bring newly to the diagnosis and treatment of patients with lung cancer Breach.Due to it has now been found that targeted therapy to the office of the distribution of the limitation of target spot and its crowd exception It is sex-limited, therefore effective target user's range of relevant treatment method is relatively narrow, there is the tumour growth mistakes that can not change at present The factors such as heterogeneous and drug resistance in journey, so the therapeutic effect of lung cancer is still faced with stern challenge at present.
Nowadays lung cancer research hotspot field is gradually horizontal toward the relevant Molecular Detection of lung cancer therapy, find new therapy target and Accurate targeted therapy direction transfer.Research report, genome at least 90%DNA is transcribed, but wherein encoding egg white gene DNA sequence Column only account for about the 2% of whole genome sequence, and most of transcript is 1ncRNA (long-chain non-coding RNA).LncRNA refers to length Degree is greater than the non-coding RNA of 200bp, and further research confirms, 1ncRNA cell Proliferation, cell differentiation, chromosome silencing, Play a key effect (Ponting CP, Oliver PL, Reik W Evolution in the biological processes such as histone modification And functions of long noncoding RNAs.Cell.2009.136 (4): 629-41.), also develop with disease and cease Manner of breathing closes.Gene relevant to adenocarcinoma of lung is found, the molecular marker for more having prospect and value is sought, for the hair for disclosing adenocarcinoma of lung Interpretation of the cause, onset and process of an illness system realizes that the early diagnosis of adenocarcinoma of lung has great importance.
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 genes relevant to adenocarcinoma of lung occurrence and development Marker realizes the early diagnosis and precision treatment of adenocarcinoma of lung using the gene marker.
To achieve the goals above, the present invention adopts the following technical scheme:
The present invention provides a kind of purposes of LINC02154 gene, are used to prepare the product of early diagnosis adenocarcinoma of lung.
Further, the product includes: with RT-PCR, real-time quantitative PCR, in situ hybridization or gene chip diagnosis adenocarcinoma of lung Product.
Further, the product with RT-PCR diagnosis adenocarcinoma of lung includes at least a pair of of specific amplification LINC02154 base The primer of cause；The product with real-time quantitative diagnosis adenocarcinoma of lung includes at least a pair of of specific amplification LINC02154 gene Primer；The product in situ hybridization diagnosis adenocarcinoma of lung includes the probe with the nucleic acid array hybridizing of LINC02154 gene；Institute Stating with the product of gene chip diagnosis adenocarcinoma of lung includes probe with the nucleic acid array hybridizing of LINC02154 gene.
Further, it is described with real-time quantitative diagnosis adenocarcinoma of lung specific amplification LINC02154 gene primer sequence such as Shown in NO.2~3 SEQ ID.
The present invention provides a kind of product for diagnosing adenocarcinoma of lung, the product can pass through LINC02154 base in detection sample The expression of cause diagnoses adenocarcinoma of lung.
Further, the product includes chip or kit.
Further, the chip can be used for detecting multiple genes including LINC02154 gene (for example, with lung gland The relevant multiple genes of cancer) expression；The kit can be used for detecting multiple bases including LINC02154 gene Because of the expression of (for example, multiple genes relevant to adenocarcinoma of lung).
The present invention provides the purposes of LINC02154 a kind of, for screening the drug for the treatment of adenocarcinoma of lung.
The present invention provides a kind of methods of the drug candidate of screening treatment adenocarcinoma of lung, which comprises
The system expressed or containing LINC02154 is handled with substance to be screened；With
Detect the expression of LINC02154 in the system；
Wherein, if substance to be screened can increase the expression of LINC02154, show that the substance to be screened is treatment lung The drug candidate of gland cancer.
The present invention provides a kind of purposes of LINC02154 gene, are used to prepare the pharmaceutical composition for the treatment of adenocarcinoma of lung.
Further, described pharmaceutical composition includes the promotor of LINC02154.
Further, described pharmaceutical composition further includes and its other medicine class of the promotor compatibility and pharmaceutically acceptable Carrier and/or auxiliary material.
The advantages of the present invention:
Human lung adenocarcinoma provided by the present invention is diagnosed with lncRNA marker, it can be achieved that the early diagnosis of adenocarcinoma of lung.
Human lung adenocarcinoma lncRNA marker provided by the present invention, can be used as potential drug target spot, be applied to clinically The treatment of adenocarcinoma of lung.
Detailed description of the invention
Fig. 1 is the expression figure using QPCR detection LINC02154 gene in pulmonary adenocarcinoma.
Specific embodiment
The present invention after extensive and in-depth study, by high throughput method, detects lncRNA in adenocarcinoma of lung sample and is swelling The expression of tumor tissue and cancer beside organism, lncRNA segment of the discovery wherein with notable difference expression, inquires into itself and adenocarcinoma of lung Relationship between generation, so that the early detection and targeted therapy for adenocarcinoma of lung find better approaches and methods.By screening, Present invention firstly discovers that LINC02154 conspicuousness is lowered in adenocarcinoma of lung.
LINC02154 in the present invention includes wild type, saltant type or its segment, as long as can incite somebody to action when carrying out sequence alignment It, which is compared, arrives known LINC02154 (gene I/D: 109729169).In the present invention, a kind of representative people The nucleotide sequence of LINC02154 gene is as shown in SEQ ID NO.1.
LINC02154 nucleotide full length sequence or its segment of the invention can usually use PCR amplification method, recombination method or people Work synthetic method obtains.It, can be according to published related nucleotide sequence, especially open reading frame for PCR amplification method Sequence carrys out design primer, and with the commercially available library cDNA or by the library cDNA prepared by conventional method well known by persons skilled in the art As template, expands and obtain related sequence.When sequence is longer, it is often necessary to carry out twice or repeatedly PCR amplification, then again will Each time the segment amplified is stitched together by proper order.
Once obtaining related sequence, so that it may obtain related sequence in large quantity with recombination method.This is usually will It is cloned into carrier, then is transferred to cell, then the isolated related sequence from the host cell after proliferation by conventional method. In addition, related sequence can be also synthesized with artificial synthesized method, when especially fragment length is shorter.In general, by first synthesizing Then multiple small fragments are attached the very long segment of available sequence again.
It is optimized for obtaining gene of the invention using round pcr DNA amplification/RNA method.Primer for PCR It can be properly selected according to the sequence information of invention disclosed herein, and available conventional method synthesis.Conventional method can be used The DNA/RNA segment of amplification is such as separated and purified by gel electrophoresis.
The present invention can use any method known in the art measurement gene expression.Those skilled in the art should manage Solution, the means for measuring gene expression are not importances of the invention, are carried out quantitatively as long as LINC02154 may be implemented.
Chip, kit
The lncRNA chip of the invention includes: solid phase carrier；And it is orderly fixed on the solid phase carrier Oligonucleotide probe, the oligonucleotide probe some or all of specifically correspond to shown in LINC02154 sequence. " probe " refers to can be with the molecule in conjunction with the particular sequence of another molecule or subsequence or other parts.Unless otherwise indicated, " visiting Needle " is often referred to that the polynucleotides combined with another polynucleotides (often referred to as " target polynucleotide ") can be matched by complementary base Probe.According to the stringency of hybridization conditions, probe energy and in conjunction with the target polynucleotide that the probe lacks sufficient sequence complementarity. Probe can make direct or indirect label, and range includes primer.Crossing system includes, but are not limited to: solution phase, is mixed at solid phase Close phase or in situ hybridization measuring method.
Specifically, can lncRNA according to the present invention, design suitable probe, be fixed on solid phase carrier, shape At " oligonucleotide arrays "." oligonucleotide arrays " refer to (addressable i.e. with distinctive with addressable point The position that address is characterized) array, each addressable point is containing a coupled characteristic oligonucleotides.According to It needs, oligonucleotide arrays can be divided into multiple sub- battle arrays.
In the present invention for LINC02154 gene oligonucleotide probe 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 spy for the length of the probe The opposite sex combines, and any length is ok.The length of the probe can be as short as 25,20,15,13 or 10 bases longs.Equally, institute The length for stating probe can be grown to 60,80,100,150,300 base-pairs or longer or even whole genes.Due to different probes Length has different influences to hybridization efficiency, signal specificity, and the length of the probe is typically at least 14 base-pairs, longest 30 base-pairs are usually no more than, the length complementary with purpose nucleotide sequence is best with 15-25 base-pair.The probe is certainly Body complementary series is most preferably less than 4 base-pairs, in order to avoid influence hybridization efficiency.
The various common used materials in genetic chip field can be used in heretofore described solid phase carrier, for example including but be not limited to Plastic products, microparticle, membrane carrier etc..The plastic products can be anti-by non-covalent or physical absorption mechanism and antibody or albumen Original combines, and most common plastic products are small test tube, globule and micro-reaction plate made of polystyrene；The microparticle is The microballoon or particle aggregated by high polymer monomer, diameter are mostly micron, due to can with the functional group in conjunction with protein, Chemical coupling easily is formed with antibody (antigen), binding capacity is big；The membrane carrier includes nitrocellulose filter, glass fibre element film And the miillpore filters such as nylon membrane.
The conventional manufacturing method of biochip known in the art can be used in the preparation of the LINC02154 chip.Example Such as, if solid phase carrier is using modification slide or silicon wafer, 5 ' ends of probe are gone here and there containing amido modified poly- dT, can be by few core Thuja acid probe is configured to solution, then using point sample instrument by its point modification slide or silicon wafer on, be arranged in scheduled sequence or Then array is fixed by standing overnight, so that it may obtain lncRNA chip of the invention.
The present invention provides a kind of kit, the kit can be used for detecting the expression of LINC02154.Preferably, institute Also containing the marker for labeled RNA sample, and substrate corresponding with the marker in the preparation or kit stated. In addition, may also include in the kit for various reagents needed for extracting RNA, PCR, hybridization, colour developing etc., including but not It is limited to: extract, amplification liquid, hybridization solution, enzyme, comparison liquid, developing solution, washing lotion etc..In addition, further including making in the kit Software is analyzed with specification and/or chip image.
Promotor and pharmaceutical composition
Based on discovery of the invention, the present invention provides a kind of pharmaceutical composition, described pharmaceutical composition includes The promotor of LINC02154.The promotor can promote the expression of LINC02154, to inhibit adenocarcinoma of lung.It is described LINC02154 promotor includes that LINC02154 gene expression product, promoted type transcription regulatory factor or promoted type target small point Sub- compound.
As a kind of preferred embodiment of the invention, the promotor of the LINC02154 is a kind of containing LINC02154 Expression vector.The expression vector is usually also containing promoter, replication orgin and/or marker gene etc..
In general, these promotors can be formulated in nontoxic, inert and pharmaceutically acceptable aqueous carrier medium, Wherein pH is usually about 5-8, and preferably pH is about 6-8, although pH value can be with the property and disease to be treated for being formulated substance Disease and be varied.Prepared pharmaceutical composition can be administered by conventional route, including (but being not limited to): Tumor is interior, intramuscular, peritonaeum is interior, intravenous, subcutaneous, intradermal or local administration.
Method well-known to those having ordinary skill in the art can be used to construct the required expression vector of the present invention.These methods include Recombinant DNA technology in vi, DNA synthetic technology, In vivo recombination technology etc..The expression vector preferably includes one or more Selected marker, to provide the phenotypic character for selecting the host cell of conversion, such as kalamycin, gentamicin, tide Mycin, amicillin resistance.
In the present invention, term " sample " is with the use of its broadest sense.In a kind of meaning, it is intended that including from it is any come The sample or culture that source obtains, and biology and environmental samples.Biological sample available from animal (including people) and cover liquid, Solid, tissue and gas.Biological sample includes blood product, blood plasma, serum etc..However, such sample should not be construed as Limitation is suitable for the invention sample type.
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.Test method without specific conditions in embodiment, usually according to conventional strip Part, such as Sambrook et al., molecular cloning: laboratory manual (New York:Cold Spring HarborLaboratory Press, 1989) condition described in, or according to the normal condition proposed by manufacturer.
Embodiment 1 screens gene marker relevant to adenocarcinoma of lung
1, sample collection
Collect the operation sample of the cancer beside organism of 4 pulmonary adenocarcinomas and pairing respectively, all patients are before surgery not Receive chemotherapy, radiotherapy, targeted therapy, immunotherapy of tumors and other treatment, without other tumor diseases, autoimmune disease and Serious chronic disease, all patients informed consent, and pass through the agreement of the committee, organizational ethics.
2, the preparation of RNA sample
It is shredded with scissors tissue, 1ml Trizol is added, shakes 1min on oscillator；Room temperature 10min, makes nucleoprotein Body decomposes completely；Then 200 μ l chloroforms (chloroform) are added, cover tightly pipe lid, acutely shake 15s, after room temperature stands 10min, 4 DEG C, 11000rpm is centrifuged 15min；Water sample layer is transferred in a new centrifuge tube, 500 μ l isopropanols are added；It is mixed by inversion Afterwards, room temperature stands after 10min 4 DEG C, and 11000rpm is centrifuged 15min；Liquid is carefully siphoned away with rifle, stays and is deposited in tube bottom, 1ml is added 75% ethyl alcohol shakes 5s on the oscillator, and washing precipitating is primary, and 4 DEG C, 8000rpm is centrifuged 5min；Then supernatant is carefully gone Fall, drying precipitated 10min, suitable water dissolution precipitating 10min is added.
3, total serum IgE is quantitative and purity analysis
The RNA of extraction is subjected to agarose gel electrophoresis, using Nanodrop2000 to the concentration of mentioned RNA and purity into Row detection, agarose gel electrophoresis detect RNA integrality, and Agilent2100 measures RIN value.5 μ of single requirement for construction data base RNA total amount G, concentration >=200ng/ μ L, OD260/280 is between 1.8~2.2.
4, construction cDNA library
The rRNA in total serum IgE is removed using Ribo-Zero kit；It is using metal ion that complete RNA is random It is broken into the small fragment of 200bp or so；CDNA text is carried out using the TruseqTM RNA sample Prep Kit of Illumina The building in library.
5, it is sequenced
Using Illumina X-Ten microarray dataset, 2*150bp sequencing is carried out.
6, high-throughput transcript profile sequencing data analysis
Bioinformatic analysis is carried out to sequencing result, after deleting the lncRNA for being not easy to detect, uses R-3.3.3 tool DESeq2 carry out Differential expression analysis, differential expression lncRNA screening criteria: FDR < 0.05, abs (log2FC)>2。
7, result
The results show that expression of the LINC02154 in pulmonary adenocarcinoma is significantly lowered compared with cancer beside organism.
The differential expression of 2 QPCR sequence verification LINC02154 gene of embodiment
1, large sample QPCR verifying is carried out to LINC02154 gene differential expression.According to the sample collection side in embodiment 1 Formula selects pulmonary adenocarcinoma and corresponding cancerous tissue each 33.
2, RNA extraction step is the same as embodiment 1
3、QPCR
1) reverse transcription reaction
LncRNA reverse transcription is carried out using FastQ μ ant the first chain of cDNA synthetic agent box (article No.: KR106), is gone first Except genomic DNA reacts, 5 × gDNA B μ ffer, 2.0 μ l is added in test tube, 1 μ g of total serum IgE adds Rnase Free ddH2O Make total volume to 10 μ l, 42 DEG C of heating 3min in water-bath, then by 10 × Fast RT B μ ffer, 2.0 μ l, RT Enzyme 1.0 μ l, FQ-RT Primer Mix of Mix, 2.0 μ l, RNase Free ddH2O5.0 μ l, is added one in above-mentioned test tube after mixing Play mixing totally 20 μ l, 42 DEG C of heating 15min, 95 DEG C of heating 3min in water-bath.
2) design of primers
QPCR amplimer is designed according to the coded sequence of LINC02154 gene and GAPDH gene in Genebank, specifically Primer sequence is as follows:
LINC02154 gene:
Forward primer is 5 '-AGAAGCCACTAACCAATG-3 ' (SEQ ID NO.2)；
Reverse primer is 5 '-TCAAGAACCAGCACTATG-3 ' (SEQ ID NO.3).
GAPDH gene:
Forward primer is 5 '-AATCCCATCACCATCTTCCAG-3 ' (SEQ ID NO.4)；
Reverse primer is 5 '-GAGCCCCAGCCTTCTCCAT-3 ' (SEQ ID NO.5).
3) QPCR amplification is examined
It with SuperReal PreMix Plus (SYBR Green) (article No.: FP205), is expanded, experimental implementation is by production Product specification carries out.
Using 20 μ l reaction systems: 2 × SuperReal PreMix Plus 10 μ l, each 0.6 μ of forward and reverse primer (10 μM) L, 5 × ROX Reference Dye△2 μ l, 2 μ l of DNA profiling, 4.8 μ l of sterile purified water.3 parallel pipes are arranged in each sample, All amplified reactions are repeated three times the above reliability to guarantee result.
Amplification program are as follows: 95 ° of 15min, (95 DEG C of 10s, 55 DEG C of 30s, 72 DEG C of 32s) × 40 circulations.
4) sample RealTime PCR is detected
2 μ l will be taken to make template after 10 times of each sample cDNA dilutions, respectively with target gene primer and reference gene primer into Row amplification.Simultaneously in 60-95 DEG C of progresss solubility curve analysis, purpose band is determined by melt curve analysis analysis and electrophoresis, 2-ΔΔCT Method carries out relative quantification.
4, result
For QPCR result as shown in Figure 1, compared with cancer beside organism, LINC02154 expresses downward, difference in pulmonary adenocarcinoma With statistical significance (P < 0.05)；What wherein expression was lowered has 33, prompts LINC02154 in the diagnosing and treating of adenocarcinoma of lung In application value with higher.
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
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<210> 5
<211> 19
<212> DNA
<213>artificial sequence (Artificial Sequence)
<400> 5
gagccccagc cttctccat 19

Claims (10)

1. a kind of purposes of LINC02154 gene, which is characterized in that be used to prepare the product of early diagnosis adenocarcinoma of lung.
2. purposes according to claim 1, which is characterized in that the product includes: with RT-PCR, real-time quantitative PCR, original The product of position hybridization or gene chip diagnosis adenocarcinoma of lung.
3. purposes according to claim 2, which is characterized in that the product with RT-PCR diagnosis adenocarcinoma of lung includes at least The primer of a pair of of specific amplification LINC02154 gene；The product with real-time quantitative diagnosis adenocarcinoma of lung includes at least a pair The primer of specific amplification LINC02154 gene；It is described in situ hybridization diagnosis adenocarcinoma of lung product include and LINC02154 base The probe of the nucleic acid array hybridizing of cause；The product with gene chip diagnosis adenocarcinoma of lung includes the core with LINC02154 gene The probe of acid sequence hybridization.
4. purposes according to claim 3, which is characterized in that the specific amplification with real-time quantitative diagnosis adenocarcinoma of lung The primer sequence of LINC02154 gene is as shown in NO.2~3 SEQ ID.
5. a kind of product for diagnosing adenocarcinoma of lung, which is characterized in that the product can pass through LINC02154 gene in detection sample Expression diagnoses adenocarcinoma of lung.
6. product according to claim 5, which is characterized in that the product includes chip or kit.
7. a kind of purposes of LINC02154, which is characterized in that for screening the drug candidate for the treatment of adenocarcinoma of lung.
8. a kind of method of the drug candidate of screening treatment adenocarcinoma of lung, which is characterized in that the described method includes:
The system expressed or containing LINC02154 is handled with substance to be screened；With
Detect the expression of LINC02154 in the system；
Wherein, the candidate substances can increase the expression of LINC02154, then show that the substance to be screened is treatment adenocarcinoma of lung Drug candidate.
9. a kind of purposes of LINC02154 gene, which is characterized in that be used to prepare prevention or treat the pharmaceutical composition of adenocarcinoma of lung Object.
10. purposes according to claim 9, which is characterized in that described pharmaceutical composition includes the promotion of LINC02154 Agent.
CN201910438450.1A 2019-05-24 2019-05-24 Purposes of the gene marker in adenocarcinoma of lung diagnosis and treatment Pending CN110093423A (en)

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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN111471767A (en) * 2020-04-09 2020-07-31 徐州市中心医院 L INC02154 and its application in preparing products for diagnosing lung cancer
CN111518905A (en) * 2020-05-09 2020-08-11 三六三医院 Application of lncRNA in diagnosis and treatment of lung adenocarcinoma
CN112662770A (en) * 2020-12-29 2021-04-16 北京泱深生物信息技术有限公司 Combined marker for lung cancer detection, detection product and application thereof

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
ABRAMSON CANCER CENTER, UNIVERSITY OF PENNSYLVANIA: "The Cancer LncRNome Atlas", 《52.25.87.215/TCLA.INDEX.PHP》 *
XU G ET AL: "Long noncoding RNA expression profiles of lung adenocarcinoma ascertained by microarray analysis", 《PLOS ONE》 *
YAN X ET AL: "Comprehensive genomeic characterization of long non-coding RNAs across human cancers", 《CANCER CELL》 *
贺帅 等: "不同类型肺癌患者血清肿瘤标志物的表达及其意义", 《海南医学》 *

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN111471767A (en) * 2020-04-09 2020-07-31 徐州市中心医院 L INC02154 and its application in preparing products for diagnosing lung cancer
CN111518905A (en) * 2020-05-09 2020-08-11 三六三医院 Application of lncRNA in diagnosis and treatment of lung adenocarcinoma
CN112662770A (en) * 2020-12-29 2021-04-16 北京泱深生物信息技术有限公司 Combined marker for lung cancer detection, detection product and application thereof

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Application publication date: 20190806