CN110106252A - Cancer diagnosis molecular marker - Google Patents
Cancer diagnosis molecular marker Download PDFInfo
- Publication number
- CN110106252A CN110106252A CN201910529535.0A CN201910529535A CN110106252A CN 110106252 A CN110106252 A CN 110106252A CN 201910529535 A CN201910529535 A CN 201910529535A CN 110106252 A CN110106252 A CN 110106252A
- Authority
- CN
- China
- Prior art keywords
- linc02081
- lung
- adenocarcinoma
- expression
- reagent
- 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.)
- Pending
Links
Classifications
-
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Engineering & Computer Science (AREA)
- Immunology (AREA)
- Pathology (AREA)
- Analytical Chemistry (AREA)
- Zoology (AREA)
- Genetics & Genomics (AREA)
- Wood Science & Technology (AREA)
- Physics & Mathematics (AREA)
- Biotechnology (AREA)
- Microbiology (AREA)
- Molecular Biology (AREA)
- Hospice & Palliative Care (AREA)
- Biophysics (AREA)
- Oncology (AREA)
- Biochemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
Abstract
The invention discloses cancer diagnosis molecular markers, the invention discloses molecular marker RP11-304L19.3, LINC02081 and RP11-286H15.1s relevant to adenocarcinoma of lung, when the significant up-regulation of RP11-304L19.3 or LINC02081 expression, or the significantly lower timing of RP11-286H15.1 expression, subject suffer from adenocarcinoma of lung.
Description
Technical field
The invention belongs to biomedicine fields, are related to cancer diagnosis molecular marker.
Background technique
Lung cancer is a kind of relatively high tumour of morbidity and mortality in worldwide.With diagnosing and treating level
Be continuously improved, 5 years survival rates of patients with lung cancer rise and 1.8% reach 16.8% (Howlander N, NooneAM, KrapchoM,
Et al.SEER Cancer Statistics Review [J] .National Cancer Institute, 2012,1975-
2009.), but prognosis is still very poor.According to the difference of biological characteristics, primary lung cancer divides non-small cell lung cancer (non-small
Cell lung cancer, NSCLC) and Small Cell Lung Cancer (small cell lung cancer, SCLC), wherein non-small cell
There are about 80%-85% for lung cancer.Epidemiological survey discovery adenocarcinoma of lung is the relatively conventional seed type in primary lung cancer, lung gland
Cancer difference parting all shows different in iconography and pathology.The investigation discovery of U.S.'s epidemiology of lung cancer, adenocarcinoma of lung account for
Lung cancer total prevalence rate about 40% or so becomes the highest lung cancer of U.S.'s disease incidence.Adenocarcinoma of lung morbidity crowd rejuvenation gradually, and
Women population is easier to fall ill, and since adenocarcinoma of lung early stage is easily by hematogenous metastasis, therefore lung is compared in clinical therapeutic efficacy and prognosis
Squamous carcinoma is poor.Therefore exploring adenocarcinoma of lung pathogenesis is particularly important, and studies early diagnosis, targeted therapy and the monitoring of adenocarcinoma of lung
Tumor associated marker is scientific research and the clinical key points and difficulties for many years studied, and the research direction of adenocarcinoma of lung from now on.
As the understanding of the complexity of human transcription group deepens continuously, the function potentiality of 1ncRNA are had occurred in researchers
The identification of revolutionary transformation, the synthesis map of the transcript of cell expression shows that the function of 1ncRNAs is sufficiently complex, and it is made
With mechanism can have due to its different structure apparent difference (Kim T, Croce C M.Long noncoding RNAs:
Undeciphered cellular codes encrypting keys of colorectal cancer pathogenesis
[J].Cancer Lett,2018.).As research deepens continuously, 1ncRNA has been found to take part in various biological process
Regulatory mechanism, such as gene expression, genomic imprinting, epigenetics are adjusted, cell Proliferation, and Apoptosis breaks up, migration
And/or intrusion, mRNA montage process, also take part in human embryos development, tissue differentiation.And the imbalance of 1ncRNA is found and more
Kind human diseases is related, such as cancer, cardiovascular disease and neurodegenerative disease etc. (Sallam T, Sandhu J,
Tontonoz P.Long Noncoding RNA Discovery in Cardiovascular Disease:Decoding
Form to Function[J].Circ Res,2018,122(1):155-66.).With long-chain non-coding RNAs certain in cancer
Unconventionality expression discovery, the more concern that researchers act on it in cancer occurrence and development, and new for tumour at present
The discovery and exploration of type molecular marker are again very urgent, so that 1ncRNA suddenly becomes research heat in the effect of tumor area
Point.
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 with characterization adenocarcinoma of lung molecular marker,
May determine that whether subject suffers from adenocarcinoma of lung and suffer from the risk of adenocarcinoma of lung by the level of detection molecules marker.
To achieve the goals above, the present invention passes through high throughput method, and lncRNA is in tumor group in detection adenocarcinoma of lung sample
The expression with normal tissue is knitted, discovery is wherein with the lncRNA of obvious differential expression, to be the diagnosing and treating of adenocarcinoma of lung
New strategy is provided, while providing theory to disclose the pathogenesis of adenocarcinoma of lung.
The present invention provides the detection molecules marker of adenocarcinoma of lung, molecular marker be selected from RP11-304L19.3,
One or more of LINC02081 or RP11-286H15.1.
The present invention provides molecular marker RP11-304L19.3, LINC02081 or RP11-286H15.1 to examine in preparation
Application in the product of disconnected adenocarcinoma of lung.
Further, when RP11-304L19.3 or LINC02081 expression up-regulation or RP11-286H15.1 expression are lowered
When, subject suffers from adenocarcinoma of lung.
Further, the product includes the reagent for detecting RP11-304L19.3, LINC02081 or RP11-286H15.1.
Further, the reagent is selected from: specific recognition RP11-304L19.3, LINC02081 or RP11-286H15.1
Probe；Or the primer of specific amplification RP11-304L19.3, LINC02081 or RP11-286H15.1.
Further, the primer sequence of specific amplification RP11-304L19.3, LINC02081 or RP11-286H15.1 is such as
Shown in SEQ ID NO.1-6.
The present invention provides it is a kind of diagnose adenocarcinoma of lung product, the product include detection RP11-304L19.3,
The reagent of LINC02081 or RP11-286H15.1.
Further, the product includes chip, kit.
Further, the reagent include reverse transcription PCR, real-time quantitative PCR, in situ hybridization, northern blotting,
The reagent of chip or high-flux sequence detection of platform RP11-304L19.3, LINC02081 or RP11-286H15.1.
Further, with the reagent of real-time quantitative PCR detection RP11-304L19.3, LINC02081 or RP11-286H15.1
Including at least the primer of a pair of of specific amplification RP11-304L19.3, LINC02081 or RP11-286H15.1.
Further, the primer sequence of specific amplification RP11-304L19.3, LINC02081 or RP11-286H15.1 is such as
Shown in SEQ ID NO.1-6.
The present invention provides application of the molecular marker in the computation model of building prediction adenocarcinoma of lung, the molecular markers
Object is selected from one or more of RP11-304L19.3, LINC02081 or RP11-286H15.1.
The present invention provides application of the molecular marker in the drug of preparation treatment adenocarcinoma of lung, the molecular marker choosing
From one or more of RP11-304L19.3, LINC02081 or RP11-286H15.1.The drug includes RP11-
The inhibitor of 304L19.3 or LINC02081 or the promotor of RP11-286H15.1 and pharmaceutically acceptable carrier.
The pharmaceutically acceptable carrier include but is not limited to diluent, adhesive, surfactant, Humectant, absorption carrier,
Lubricant, filler, disintegrating agent.
In the present invention, people RP11-304L19.3, LINC02081 and RP11-286H15.1 gene be located at 16,17,
On No. 2 chromosomes, including gene and its homologue, mutation and isoform.The term covers overall length, unprocessed RP11-
304L19.3, LINC02081 and RP11-286H15.1, and from any type of RP11- processed in cell
304L19.3, LINC02081 and RP11-286H15.1.The term covers RP11-304L19.3, LINC02081 and RP11-
The natural generation variant (such as splice variant or allelic variant) of 286H15.1.As unrestricted example, RP11-
304L19.3 sequence such as ENST00000565937.1
It is shown；As unrestricted example, the sequence of LINC02081 such as NR_110848.1, NR_110849.1 is any
Shown in transcript.In the present invention, a kind of sequence of representative LINC02081 is as shown in NR_110848.1；As unrestricted
The example of property, the sequence of RP11-286H15.1 is as shown in ENST00000609697.1.
Those skilled in the art will be seen that, when carrying out bioinformatic analysis to sequencing result, it will usually will
Sequencing result and known genome are compared, as long as sequencing fragment can compare on relevant gene, so that it may regard as
It is the expression of the gene, therefore, the different transcription products of RP11-304L19.3, LINC02081 and RP11-286H15.1 are same
Sample includes in the present invention.
It will be appreciated by those skilled in the art that the means of measurement gene expression are not importances of the invention.It can be
The expression of biomarker is detected on transcriptional level.The present invention can use any method known in the art measurement base
Because of expression.
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 LncRNA, one or more biologies of the invention in a sample
The difference of one or more splice variant expressions of the RNA of the marker and/or biomarker lncRNA.Difference table
Up to can it is as described herein and those skilled in the art understand that method determine.Term " differential expression " or " change of expression
Change " indicate with biomarker given in second of sample measure expression compared with, the amount of RNA after measured, in sample
Given biomarker can measure increasing or decreasing for expression.Term " differential expression " or " variation of expression " may be used also
With indicate in second sample group biomarker measure expression compared with, in sample group give biomarker can
Measurement expression increases or decreases." differential expression " used herein can be opposite with the expression of given biomarker
The ratio that the Average expression level of biomarker is given in control is measured, and wherein ratio is not equal to 1.0.It can also use
P value measures differential expression.When using p value, when p value is less than 0.1, biomarker is accredited as in the first and second groups
Between differential expression.More preferable p value is 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
It is preferred that p value is less than 0.001.When sketch-based user interface determines differential expression, if expression in the first and second of sample
Ratio is more than or less than 1.0, then RNA is differential expression.For example, the ratio greater than 1.2,1.5,1.7,2,3,4,10,20
Rate, or the ratio less than 1, such as 0.8,0.6,0.4,0.2,0.1,0.05.In another embodiment of the present invention, if
The ratio of the Average expression level of first group and the Average expression level of the second group is more than or less than 1.0, then transcribed nucleic acid
It originally 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, such as
0.8,0.6,0.4,0.2,0.1,0.05.In another embodiment of the present invention, if expression in first sample
Be more than or less than 1.0 with the ratio of Average expression level in second colony, be greater than 1.2 for example including ratio, 1.5,1.7,2,
3,4,10,20 or 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 (with rna expression) is shown
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 measured) with rna expression
Display reduces at least 10% or more, such as 20%, 30%, 40% or 50%, 60%, 70%, 80%, 90% or less than 1.0
Again, 0.8 times, 0.6 times, 0.4 times, 0.2 times, 0.1 times or less gene.For example, up-regulation gene includes dividing with from normal individual
From the expression of RNA compare, the horizontal increased base of rna expression from the sample of the individual separation characterized by with adenocarcinoma of lung
Cause.For example, down-regulated gene includes compared with the sample separated from normal individual, from the individual separation characterized by with adenocarcinoma of lung
Sample in rna expression level reduce gene.
LncRNA of the invention is detected using multiple nucleic acids technology known to persons of ordinary skill in the art, including but
It is not limited to reverse transcription PCR, real-time quantitative PCR, in situ hybridization, northern blotting, chip or high-flux sequence platform.
Detection, which is carried out, with reverse transcription PCR includes at least a pair of of specific amplified RP11-304L19.3, LINC02081 or RP11-
286H15.1 the primer of gene；With real-time quantitative PCR carry out detection include at least a pair of of specific amplified RP11-304L19.3,
The primer of LINC02081 or RP11-286H15.1 gene；With in situ hybridization carry out detection include: with RP11-304L19.3,
The probe of the nucleic acid array hybridizing of LINC02081 or RP11-286H15.1 gene；It is detected at least with northern blot
Probe including the nucleic acid array hybridizing with RP11-304L19.3, LINC02081 or RP11-286H15.1 gene；With chip into
Row, which detects, includes: and the probe of the nucleic acid array hybridizing of RP11-304L19.3, LINC02081 or RP11-286H15.1 gene.
In the present invention, term " primer " is meant, is capable of forming the base-pair (base complementary with template strand
Pair), and play the role of 7~50 nucleic acid sequences of the starting point for replicating template strand.Primer is usually synthesized into,
But the nucleic acid of nature generation also can be used.The sequence of primer is it is not absolutely required to identical with the sequence of template, as long as filling
Divide complementary and can hybridize with template.The addition feature for not changing the fundamental property of primer can be mixed into.As can mix
The example of the addition feature entered has methylation, replaces modification between nucleic acid by homologue with cap, more than one nucleic acid, but
It is without being limited thereto.
Term " probe ", which refers to, is as short as several nucleic acid fragment such as RNA or DNA to up to hundreds of bases, and the nucleic acid fragment can
To establish specific binding with mRNA and can determine the presence of specific mRNA because maintaining label (Labeling) effect.It visits
Needle can be by oligonucleotide probe, single stranded DNA (singlestrandedDNA) probe, double-stranded DNA
(doublestrandedDNA) prepared by the forms such as probe and rna probe.It in the present invention, can be by using mark of the invention
Remember that polynucleotides and complementary probe implement hybridization, by whether hybridizing and predict adenocarcinoma of lung.It can be based on content known in the art
Modify the appropriate selection to probe and hybridization conditions.
Term " chip " is also referred to as " array ", refers to the solid support of the nucleic acid comprising connection or peptide probes.Array is usual
A variety of different nucleic acid or peptide probes comprising being connected to substrate surface according to different known locations.These arrays, also referred to as
" microarray " can use mechanical synthesis methods or light guidance synthetic method usually to generate these arrays, and the light guidance is closed
The combination of photolithography method and solid phase synthesis process is incorporated at method.Array may include flat surface, or can be pearl
Son, gel, polymer surfaces, the fiber of such as optical fiber, glass or nucleic acid or peptide in any other suitable substrate.It can be with
Certain mode carrys out array of packages, to allow to carry out the manipulation of diagnosis of global function device or other means.
Kit provided by the invention is used to detect the rna level of one or more biomarkers.In certain embodiment party
In case, the kit includes the one or more probes specifically bound with the RNA of one or more biomarkers.At certain
In a little embodiments, the kit also includes washing solution.In certain embodiments, the kit also includes that progress is miscellaneous
Hand over reagent, RNA isolated or purified tool, detection instrument and the positive and negative control of test.In certain embodiments, institute
State kit also and include the specification using the kit.
In a specific embodiment of the present invention, experiment be all to be completed according to being at least repeated 3 times, result data be all with
The mode of mean+SD indicates, using SPSS statistical software come for statistical analysis, difference between the two adopted
It is examined with t, it is believed that there is statistical significance as P < 0.05.
The advantages of the present invention:
Present invention firstly discovers that RP11-304L19.3, LINC02081 and RP11-286H15.1 are in the patients with lung adenocarcinoma
Differential expression, by the expression for detecting said gene, it can be determined that whether subject suffers from adenocarcinoma of lung, is the morning of adenocarcinoma of lung
Phase diagnosis provides Molecular tools.
Detailed description of the invention
Fig. 1 is using QPCR detection RP11-304L19.3, LINC02081 or RP11-286H15.1 gene in adenocarcinoma of lung group
Expression figure in knitting；The wherein expression figure that figure A is RP11-304L19.3, the expression that figure B is LINC02081
Figure, the expression figure that figure C is RP11-286H15.1.
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.Test method without specific conditions in embodiment, usually according to conventional strip
Part, or according to the normal condition proposed by manufacturer.
Embodiment 1 screens gene marker relevant to adenocarcinoma of lung
1, sample collection
Collect 31 patients with lung adenocarcinoma pulmonary adenocarcinoma and corresponding cancer beside organism, all patients are preoperative not to carry out
Chemotherapy, radiotherapy and endocrine therapy, therefrom optional 4 pairs of progress high-flux sequence, high-flux sequence are completed by Hua Da gene.
2, the preparation and quality analysis of RNA sample
Total tissue RNA is extracted using TRIZOL method, the specific steps are as follows:
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, the building and sequencing of cDNA library
The building and sequencing of cDNA library are completed by Hua Da gene, comprising steps of
1) building of cDNA library
The building that cDNA library is carried out using the TruseqTM RNA sample Prep Kit of Illumina, in reverse transcription
Under the action of enzyme, using random primer, one chain cDNA of synthesis is inverted by template of lncRNA, when carrying out the synthesis of two chains, dNTPs examination
DTTP is replaced with dUTP in agent, making base in the second chain of cDNA includes A/U/C/G；
2) machine is sequenced on
Qualified library is detected, NaOH denaturation is added at single-stranded, it is anticipated that upper machine data volume, is diluted to certain upper machine
Concentration.Library after denaturation dilution is added in FlowCell, hybridizes with the connector on FlowCell, bridge-type is completed on cBot
PCR amplification finally carries out 2*150bp sequencing using Illumina Hiseq x-ten platform.
4, bioinformatic analysis
After deleting the lncRNA for being not easy to detect, Differential expression analysis, difference are carried out using the DESeq2 of R-3.3.3 tool
Express lncRNA screening criteria: FDR < 0.05, abs (log2FC)>2。
5, result
Sequencing result shows that RP11-304L19.3, LINC02081 express up-regulation, RP11-286H15.1 in adenocarcinoma of lung
Significant downward is expressed in adenocarcinoma of lung, and RP11-304L19.3, LINC02081 and RP11-286H15.1 is prompted to can be used as possibility
Detection target be applied to adenocarcinoma of lung early diagnosis, in order to further verify high-flux sequence as a result, to above-mentioned three kinds of bases
Because carrying out QPCR verifying in 31 pairs of sample tissues of collection.
The differential expression of 2 QPCR sequence verification RP11-304L19.3, LINC02081 gene of embodiment
1, RNA is extracted
Extracted using Trizol method and RNA extraction carried out to 31 pairs of tissue samples collecting in embodiment 1, specific steps referring to
Embodiment 1.
2, reverse transcription
Carry out using the reverse transcription reagent box (Takara code:DRR047A) of TAKARA company the reverse transcription of RNA,
Experimental implementation carries out to specifications, and steps are as follows:
1) 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.
2) reverse transcription reaction
It will2 4.0 μ l of Buffer,RT Enzyme Mix I1.0 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.
3, QPCR is expanded
1) design of primers
According to the gene order design primer of RP11-304L19.3, LINC02081, RP11-286H15.1 and GADPH, sequence
It arranges as follows:
RP11-304L19.3 gene:
SEQ ID NO.1 (F): 5 '-TGAGATTACAGGCGTGAG-3 '；
SEQ ID NO.2 (R): 5 '-AGTTGGAGACAGTGAGAC-3 '.
LINC02081 gene:
SEQ ID NO.3 (F): 5 '-AATGGCGGATGTATGAAC-3 '；
SEQ ID NO.4 (R): 5 '-TGAGTTGACTGAGGTTGT-3 '.
RP11-286H15.1 gene:
SEQ ID NO.5 (F): 5 '-CGACTATAATATCCAACCGAACT-3 '；
SEQ ID NO.6 (R): 5 '-TCCCAAAGCCAGTATATGAATAG-3 '.
GAPDH gene:
SEQ ID NO.7 (F): 5 '-AATCCCATCACCATCTTCCAG-3 '；
SEQ ID NO.8:5 '-GAGCCCCAGCCTTCTCCAT-3 '.
2) QPCR amplification is examined
WithPremix Ex TaqTMII (Takara Code:DRR081) kit configures PCR reaction system,
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.
25 μ l reaction systems:Premix Ex TaqTM II (2 ×) 12.5 μ l, it is positive (anti-) to each 1 μ l of primer,
2 μ l of DNA profiling, 8.5 μ l of sterile purified water.
Reaction condition: 95 DEG C of 30s, (95 DEG C of 5s, 60 DEG C of 30s) × 40
4, result
QPCR result is as shown in Figure 1, compared with cancer beside organism, and RP11-304L19.3, LINC02081 are in pulmonary adenocarcinoma
Middle expression up-regulation, raises about 14.6 times and 7.2 times respectively, and RP11-286H15.1 expresses downward in pulmonary adenocarcinoma, lowers about
8.3 times, difference has statistical significance (P < 0.05), consistent with high-flux sequence result, prompt RP11-304L19.3,
LINC02081 and RP11-286H15.1 can be used as the diagnosing and treating that biomarker is applied to adenocarcinoma of lung.
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>People Hospital No.1, Jining City
<120>cancer diagnosis molecular marker
<160> 8
<170> SIPOSequenceListing 1.0
<210> 1
<211> 18
<212> DNA
<213>artificial sequence (Artificial Sequence)
<400> 1
tgagattaca ggcgtgag 18
<210> 2
<211> 18
<212> DNA
<213>artificial sequence (Artificial Sequence)
<400> 2
agttggagac agtgagac 18
<210> 3
<211> 18
<212> DNA
<213>artificial sequence (Artificial Sequence)
<400> 3
aatggcggat gtatgaac 18
<210> 4
<211> 18
<212> DNA
<213>artificial sequence (Artificial Sequence)
<400> 4
tgagttgact gaggttgt 18
<210> 5
<211> 23
<212> DNA
<213>artificial sequence (Artificial Sequence)
<400> 5
cgactataat atccaaccga act 23
<210> 6
<211> 23
<212> DNA
<213>artificial sequence (Artificial Sequence)
<400> 6
tcccaaagcc agtatatgaa tag 23
<210> 7
<211> 21
<212> DNA
<213>artificial sequence (Artificial Sequence)
<400> 7
aatcccatca ccatcttcca g 21
<210> 8
<211> 19
<212> DNA
<213>artificial sequence (Artificial Sequence)
<400> 8
gagccccagc cttctccat 19
Claims (10)
1. the detection molecules marker of adenocarcinoma of lung, which is characterized in that molecular marker is selected from RP11-304L19.3, LINC02081
Or one or more of RP11-286H15.1.
2. application of the molecular marker described in claim 1 in the product of preparation diagnosis adenocarcinoma of lung.
3. application according to claim 2, which is characterized in that it is raised when RP11-304L19.3 or LINC02081 is expressed,
Or RP11-286H15.1 expresses lower timing, subject suffers from adenocarcinoma of lung.
4. application according to claim 2 or 3, which is characterized in that the product include detection RP11-304L19.3,
The reagent of LINC02081 or RP11-286H15.1.
5. application according to claim 4, which is characterized in that the reagent is selected from: specific recognition RP11-
304L19.3, the probe of LINC02081 or RP11-286H15.1；Or specific amplification RP11-304L19.3, LINC02081 or
The primer of RP11-286H15.1.
6. application according to claim 5, which is characterized in that specific amplification RP11-304L19.3, LINC02081 or
The primer sequence of RP11-286H15.1 is as shown in SEQ ID NO.1-6.
7. a kind of product for diagnosing adenocarcinoma of lung, which is characterized in that the product includes detection RP11-304L19.3, LINC02081
Or the reagent of RP11-286H15.1.
8. product according to claim 7, which is characterized in that the product includes chip, kit.
9. product according to claim 7, which is characterized in that the reagent includes reverse transcription PCR, real-time quantitative PCR, original
Position hybridization, northern blotting, chip or high-flux sequence detection of platform RP11-304L19.3, LINC02081 or
The reagent of RP11-286H15.1.
10. product according to claim 9, which is characterized in that with real-time quantitative PCR detection RP11-304L19.3,
The reagent of LINC02081 or RP11-286H15.1 include at least a pair of specific amplification RP11-304L19.3, LINC02081 or
The primer of RP11-286H15.1；Preferably, specific amplification RP11-304L19.3, LINC02081 or RP11-286H15.1
Primer sequence is as shown in SEQ ID NO.1-6.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910529535.0A CN110106252A (en) | 2019-06-19 | 2019-06-19 | Cancer diagnosis molecular marker |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910529535.0A CN110106252A (en) | 2019-06-19 | 2019-06-19 | Cancer diagnosis molecular marker |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN110106252A true CN110106252A (en) | 2019-08-09 |
Family
ID=67495465
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201910529535.0A Pending CN110106252A (en) | 2019-06-19 | 2019-06-19 | Cancer diagnosis molecular marker |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN110106252A (en) |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108004322A (en) * | 2017-12-21 | 2018-05-08 | 潍坊医学院 | A kind of applications of lncRNA in adenocarcinoma of lung is diagnosed and/or treated |
| WO2018174860A1 (en) * | 2017-03-21 | 2018-09-27 | Mprobe Inc. | Methods and compositions for detection early stage lung adenocarcinoma with rnaseq expression profiling |
| CN109576371A (en) * | 2018-12-28 | 2019-04-05 | 北京泱深生物信息技术有限公司 | Application of the long-chain non-coding RNA in adenocarcinoma of lung |
-
2019
- 2019-06-19 CN CN201910529535.0A patent/CN110106252A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2018174860A1 (en) * | 2017-03-21 | 2018-09-27 | Mprobe Inc. | Methods and compositions for detection early stage lung adenocarcinoma with rnaseq expression profiling |
| CN108004322A (en) * | 2017-12-21 | 2018-05-08 | 潍坊医学院 | A kind of applications of lncRNA in adenocarcinoma of lung is diagnosed and/or treated |
| CN109576371A (en) * | 2018-12-28 | 2019-04-05 | 北京泱深生物信息技术有限公司 | Application of the long-chain non-coding RNA in adenocarcinoma of lung |
Non-Patent Citations (3)
| Title |
|---|
| LIU H等: "Long noncoding RNA TUG1 is a diagnostic factor in lung adenocarcinoma and suppresses apoptosis via epigenetic silencing of BAX", 《ONCOTARGET》 * |
| WANG Y等: "Screening key lncRNAs for human lung", 《CANCER BIOMARK》 * |
| 李 楠等: "TCGA 数据库中肺腺癌标志物的数据发掘研究", 《实用医药杂志》 * |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US20100286044A1 (en) | Detection of tissue origin of cancer | |
| KR101504817B1 (en) | Novel system for predicting prognosis of locally advanced gastric cancer | |
| JP2015511121A (en) | Breast cancer biomarker signature for invasiveness and prognosis | |
| CA2859021A1 (en) | Methods and kits for detecting subjects at risk of having cancer | |
| CN109609648A (en) | LncRNA marker relevant to liver cancer and its detection primer and application | |
| CN101173313B (en) | Mammary cancer metastasis and prognosis molecule typing gene group, gene chip producing and using method | |
| CN104975019B (en) | Application of the finger-print of tiny RNA composition in human ovarian cancer diagnosing and treating | |
| CN104032001B (en) | ERBB signal pathway mutation targeted sequencing method for prognosis evaluation of gallbladder carcinoma | |
| CN104673883B (en) | For predicting the microRNA biomarker and detection method of early stage non-metastatic colorectal cancer prognosis | |
| CN109735624A (en) | Application of the gene marker in diagnosis of thyroid cancer | |
| CN102325902A (en) | Methods and means for typing a sample comprising colorectal cancer cells | |
| CN109913554A (en) | A kind of lncRNA marker relevant to breast cancer | |
| CN105671187B (en) | Group of genes for molecular typing of head and neck squamous cell carcinoma and application thereof | |
| CN110055332A (en) | Marker relevant to thyroid cancer and its application | |
| CN110093423A (en) | Purposes of the gene marker in adenocarcinoma of lung diagnosis and treatment | |
| US20220372578A1 (en) | Urine mirna fingerprint for detecting bladder and urothelial carcinoma and application thereof | |
| CN110628914B (en) | LncRNA marker related to breast cancer, detection primer and application thereof | |
| CN110452989B (en) | Application of biomarker in detection and diagnosis of gastric cancer | |
| CN105985955B (en) | Application of fingerprint composed of small RNA in gastric cancer | |
| CN110093422A (en) | Application of the LINC02159 in adenocarcinoma of lung diagnosis and treatment | |
| CN110106252A (en) | Cancer diagnosis molecular marker | |
| CN110305961B (en) | Application of miR-1207 and target gene thereof in detection of laryngeal squamous cell carcinoma | |
| CN110042164B (en) | Lung cancer diagnosis and treatment lncRNA marker | |
| CN109439743A (en) | A kind of biomarker of severe asthma and its application | |
| CN110117656A (en) | A kind of biomarker relevant to sdenocarcinoma of stomach occurrence and development |
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 | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20190809 |
|
| RJ01 | Rejection of invention patent application after publication |