CN107460238A - A kind of noninvasive high flux methylates prostate cancer diagnosis, research and treatment method - Google Patents
A kind of noninvasive high flux methylates prostate cancer diagnosis, research and treatment method Download PDFInfo
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Abstract
Noninvasive high flux methylates prostate cancer diagnosis, research and treatment method, it is characterised in that and combined based on big Flux DNA methylation assay and be sequenced and heal the cfRNA information in liquid, the change to be methylated in the identification gene related to carcinoma of prostate：Detect the presence or absence of DNA methylation in sample gene, to produce methylome, establish SOBP, SUCLG2, SHOX2, the specific C pG islands site that ZDHHC1 genes contain, identifies and is attached to the DNA fragmentation to methylate with specific anti-methlycytosine antibody, and methylate two generation sequencing libraries and target site enrichment are established using immunoprecipitate；And by methylome compared with standard spectrum, whether " waterfall " Analysis on Mechanism, which has cancer, is utilized to methylation sites sequencing biological information, the calculating comprehensive analysis of gene information and methylation sites in conjunction with cfRNA, being capable of prostate organs or the tumour at position in early detection human body.
Description
Technical field
The present invention relates to the detection of biotechnology gene methylation, specifically a kind of noninvasive high flux prostate cancer that methylates is examined
Disconnected, research and treatment method.
Background technology
In recent years, epigenetics research has become a new direction of cancer research.Nineteen eighty-three, scientists are first
It was found that there is close relationship between DNA methylation and cancer.The difference of each CpG sites methylation state on genomic DNA
Genomic DNA methylation level spectrum is formed, genomic DNA abnormal methylation can cause the occurrence and development of a variety of diseases of the mankind.Largely
Result of study shows, abnormal change and the cancer of epigenetic modification have it is very close contact, in the range of full-length genome
Epigenetic modification changes the new mark for having become cancer.Newest viewpoint thinks, the occurrence and development of cancer not only with something lost
Pass and change correlation, the abnormal change of epigenetic modification also extends through each stage in cancer.Therefore, this means that cancer exists
It is a kind of epigenetic disease to a certain extent.Important component of the DNA methylation as epigenetic modification, it is in cancer
The research of early diagnosis, treatment, prognosis and prevention etc. also achieve corresponding achievement.The World Health Organization points out,
/ 3rd cancer can prevent, and 1/3rd cancer can treat, and want to prevent and treat, and just have to examine in early days
Disconnected, early diagnosis, early treatment can not only save a large amount of costs, and prior is the survival rate for greatly improving patient.It is existing
It is to be directed to gene mutation or restructuring in most tumors detection, has directive significance (fairly simple) to medication but morning can not be detected
Phase tumour.In technical limitation up to this point, scientist and laboratory early stage sieve can only be carried out to unitary class tumour
Look into, realize that the one-time detection of this high sensitivity high precision early diagnoses the technology of all tumours, also many technologies are difficult at present
Point.The especially enrichment of target methylation sites, the total solution for the sequencing of future generation that do not methylate currently on the market.For
The deciphering of methylation sites with clinical meaning needs to obtain by a large amount of clinical researches, and these sites are for the accurate of detection
Property is most important.There is presently no the method for maturation and reliable data to understand these sequencing data.There are two problems to contain to wait to solve
Certainly, when sequencing after obtain how bulk information is analyzed, second, analysis obtain a result, with clinic whether meet, with the state of an illness whether
Meet.In a word, although DNA DNA methylation assays are generally acknowledged early-stage cancer detection methods, because current technology is in sensitivity
With the stage for all not reaching Clinical practice in accuracy.
The content of the invention
Methylated prostate cancer diagnosis, research and treatment method it is an object of the invention to provide a kind of noninvasive high flux, base
The change of methylation patterns in the sequencing technologies of future generation of high flux gene methylation, the identification gene related to carcinoma of prostate
Change, being capable of prostate organs or the tumour at position in early detection human body.
A kind of noninvasive high flux methylates prostate cancer diagnosis, research and treatment method, including but not limited to cancer mark
Thing, there is provided biological sample from subject and comprising genomic DNA, it is characterised in that methylated inspection based on big Flux
Survey combination sequencing M-NGS while add the cfRNA information in blood, methylated in the identification gene related to carcinoma of prostate
Change：The presence or absence of DNA methylation in the biological sample one or more gene of subject is detected, to produce the first of subject
Baseization is composed, including establishes SOBP, SUCLG2, SHOX2, the specific C pG islands site that ZDHHC1 genes contain, and use is specific
Anti- methlycytosine antibody identifies and is attached to the DNA fragmentation to methylate, and the effect of enrichment is reached using immunoprecipitate
Fruit, to realize the methylate foundation of two generation sequencing libraries and the enrichment of target site；And by the methylome of subject and one
Or multiple standard methylation spectrums are compared, " waterfall " mechanism is utilized to calculate comprehensive analysis methylation sites sequencing biological information
Show whether subject has the conclusion of cancer, the hair of cancer is determined with reference to the gene information from acellular ribonucleic acid cfRNA
Raw and positioning.
Outstanding contributions of the present invention：
The present invention has developed the application of the sequencing technologies of future generation based on gene methylation, is built by the enrichment of target site
Generation sequencing library is made, the gene information that obtained methylome combination cfRNA is provided can be any in early detection human body
Organ or the tumour at position.The GRAIL that the only Bill lid of infantile tumour blood examination is hereby invested is in the present U.S., but present invention side
Method is not exclusively the same with them, in addition, GRAIL does not also detect cfRNA simultaneously, it is not known that expression conditions, therefore its knot
It is affected by with clinical accuracy matching degree.And their Database is because the insufficient influence of number of patients,
Basic number of samples scale can be also restricted, therefore the GRAIL hereby invested with Bill's lid rival can be ignored.
The technology of the present invention is based on the combination sequencing of big Flux DNA methylation assay, maintains the leading position in the industry, adds simultaneously
Upper cfRNA information analysis methods.It is well known that the switch of gene must be judged by RNA, DNA methylation is upstream letter
Breath, only the two aspect information are combined, susceptibility and the degree of accuracy could all reach extraordinary degree.
We utilize " waterfall " Analysis on Mechanism to draw a conclusion methylation sites sequencing biological information first, obtain special
CpG islands site, then to all effective sites to methylate all by the contrast of clinical samples and normal specimen, according to these
The detection and analysis in site, have had 83% accuracy rate, especially for prostate on clinical specificity in prostate cancer
Cancer has reached more than 90%.In addition, the invention contains cfRNA information technologies：When only obtaining gene methylation
Information after, you do not know the expression of the gene, and cfRNA of the invention information can accurately know the expression of the gene
Situation, it is possible to the clearer change for finding gene expression, so as to more accurately determine the position of early detection canceration, to wide
It is further strengthened to compose diagnosing tumor.In short, the gene methylation technology is unique and perspective, forefront can be surveyed in early days in advance
The generation of adenoncus knurl.Current visible and available all detection methods can not all be completed, and in the market is not also specifically for morning
Phase tumor screening based on the broad-spectrum tumor next generation's sequencing scheme to methylate, we have found breach, and achieve into
Work(.
Brief description of the drawings
Fig. 1 is DNA methylation pattern display figure in prostata tissue；
Fig. 2 be prostata tissue in SOBP, SUCLG2, SHOX2, the ZDHHC1 % schematic diagrames that always methylate.
Embodiment
The noninvasive high flux of the present invention methylates prostate cancer diagnosis, research and treatment method, including but not limited to cancer
Mark, there is provided biological sample from subject and comprising genomic DNA, it is characterised in that based on big Flux methyl
Change detection combination sequencing simultaneously plus the cfRNA information in blood, identify the mould that methylated in the gene related to carcinoma of prostate
The detection method of formula：The presence or absence of DNA methylation in one or more genes of biological sample is detected, to produce subject's
Methylome, and by the methylome of subject compared with one or more standard methylations spectrum.The standard methyl
Change the methylome of methylome and carcinous sample of the spectrum selected from non-cancerous sample.
The cfRNA information technologies of the present invention：The RNA discharged using the tumour cell to dissociate in blood, can strongly be resisted
The degraded of ribalgilase in blood, and exist enough horizontal to carry out quantitative analysis this characteristic, and these
The RNA of circulation is obvious compared with Healthy People in the serum and blood plasma of cancer patient to be risen, and the gene obtained by them is believed
Breath, with reference to the result of the methylation profiles of subject, and then provides definite diagnostic result.
Noninvasive high flux of the present invention methylates the diagnostic method of carcinoma of prostate, there is provided from be diagnosed as cancer by
The biological sample of examination person, comprising genomic DNA, it is characterised in that identification gene on the CGI Dao He CpG islands of promoter region
In diagnosis marker and clinical target of the methylation level as prostate cancer；It is corresponding when methylation level increase be present
Be exactly the gene expression reduce.Specially screen subject in method existing for prostate cancer, including (a) from from by
Genomic DNA is extracted in the biological sample of examination person, bisulfite conversion then is carried out to it；Use vitro assay (b)
High flux two generations sequenator detects the gene SOBP, SUCLG2, SHOX2, ZDHHC1 methylation state, in the subject
Given the test agent in, the methylation of said gene shows methylation level relative to normal prostate cell, instruction result
Elevated is prostate cancer.
Present invention also offers a kind of further method for diagnosing cancer, the sign of cancer include determining disease exist or
The chance being not present.In further embodiment, the sign of cancer includes determining the risk that metastatic disease occurs.
In other embodiments, the sign of cancer also includes the progression of disease situation for monitoring the subject.Above-mentioned detection method is obtained
The testing result arrived, after being calculated with diagnostic method algorithm the following, the sign risk assessment of cancer is obtained, so as to provide subject
Cancer development accurate conclusion.
The invention provides the method for characterizing qualitative carcinoma of prostate, including provide from the subject's for being diagnosed as cancer
Biological sample and comprising genomic DNA, it is characterised in that detection gene methylation be in the 5` non-translational regions of gene, detection
The presence or absence of DNA methylation in SOBP, SUCLG2, SHOX2, ZDHHC1 gene, so as to characterize whether subject has cancer.
Fig. 2 shows SOBP, SUCLG2, SHOX2 in prostata tissue, and ZDHHC1's always methylates.The prostate cancer group of score ratio 21/22
Knit and show the high methylations of four genomic promoter regions with the prostate cell line of 6/6 conversion, and normal 0/3, it is benign
Adjacent tissue 0/7 or normal PrEC cells are not detected by and methylated.
The applicable object of this detection is the excessive risk male of more than 50 years old, and the platform of detection is two generation sequenators, detects this
Four genes are SOBP, SUCLG2, SHOX2, ZDHHC1.Supernatant is taken to extract dissociative DNA after 10 milliliters of centrifugal bloods.Then utilize
Bisulfite conversion are converted into the CpG islands to methylate CC sequence, then construction sequencing library carries out big flux and put down
Row sequencing.Density that gene specific region methylates is read by the analysis to sequencing result to judge whether that patient has suffered from
Prostate cancer.The methylation level of 4 gene specific regions meets following diagnosis algorithms in blood after testing, is diagnosed as early stage
Prostate cancer.In further embodiment, the negative rate of accuracy reached of this detection can effectively exclude inspection pair to 96.3%
Possibility as suffering from prostate cancer.
Biological sample of the present invention and comprising genomic DNA, in some embodiments, biological sample is biopsy
Sample.In other embodiments, biological sample is blood sample.In some embodiments, DNA methylation includes CpG first
Base.In some embodiments, DNA methylation methylates including CpG.In some preferred embodiments, DNA first is detected
The existence or non-existence of base includes digesting the genomic DNA with methylation sensitive restriction enzyme, then to containing CpG islands
DNA fragment specific carries out polygenic amplification.In some embodiments, methods described also includes detecting one or more genes
The middle possibility to be methylated presence or absence of DNA, including SI 00, SRBC, RalGDS, HDSfl, Sy, Cyclin D2,
TMS1, HIC-1, hMLHl, Rab6c, E-cadherin, 14-3-3sigma, IGF2, SFRP5 and MDGI.In some embodiment party
In case, subject is in the excessive risk state for developing into cancer.Embodied by counting in Fig. 1, in shown prostata tissue
DNA methylation pattern：Compared with CGI is located at methylating in other genome areas, the percentage that methylates in promoter CGI
Than gradually increase.
In some embodiments, it is quick to include methylating for genomic DNA of the digestion containing one or more genes for reagent
Perceptual Restriction Enzyme, methylation sensitive restriction enzyme include Hin 61；In other embodiments, methylation sensitive restriction enzyme
Include HpaH.In a further embodiment, characterizing cancers include determining the risk that metastatic disease occurs.In other embodiment party
In case, characterizing cancers include the progression of disease of monitoring subject.
Methylate the sequencing of two generations
A. the genomic DNA 5 micrograms separated from LNCaP cells be ultrasonically treated to100-500bp scopes, and use
Qiagen PCR purification kits are purified.B. repair end using the Illumina schemes of standard, by poly A afterbodys and
Adapter is added in piece segment DNA.C. and then by the piece segment DNA in 95 DEG C of thermal denaturations 10 minutes, and in quick cooling on ice.d.
The anti-methlycytosine antibody of 5 micrograms in DNA and IP buffer solutions is incubated overnight for 4 DEG C in an oscillator.E. by with it is 100 micro-
Rise Protein A resin bead to be incubated 2 hours at 4 DEG C, collect methylation fragment.F. Protein A resin bead is being immunized at 4 DEG C
Wash 4 times, and be resuspended in 200 microlitres of TE buffer solutions containing 0.25%SDS and 5 micrograms of protein enzyme K in precipitation IP buffer solutions,
And it is incubated 2 hours at 55 DEG C.G. DNA Clean and Concentrator-5 kits samples are used, according to
Illumina ChIP-Seq schemes prepare library.H. quantify the library using Bio-Analyzer, and each library is used
10nM concentration prepares the flow cell per the cluster of swimming lane about 30,000.
Diagnostic method algorithm：The change for characterizing gene SOBP, SUCLG2, SHOX2, ZDHHC1 DNA methylation pattern will
Calculated with following formula：
Diagnose Zong CpG islands in total methylated CpG island/4 gene in the gene of hazards=4
If this numeral is less than 0.15, patient is just without any prostate cancer risk.
If for this numeral between 0.15-0.3, the risk that patient is diagnosed as early-stage cancer is very high.
If this numeral is more than 0.3, then the risk that patient is diagnosed as the T2 phases or more is very high.
Interpretation technique noun：High throughput sequencing technologies are the changes to tradition sequencing revolution, once to hundreds of thousands
Sequencing is carried out to millions of DNA moleculars, therefore is called of future generation or two generation sequencing technologies next generation
Sequencing, while high-flux sequence causes the analysis of transcript profile and the careful overall picture of genome progress to a species to turn into
May, so the deep sequencing deep sequencing that are otherwise known as.
Bio-Analyzer bioanalysis agent is Agilent Technologies, Santa Clara, California.
IP buffer solutions are the 10mM sodium phosphate buffers containing 100-200mM sodium chloride and 0.02-1.0%Triton X-100
Liquid.
Protein A resin pearl bead comes from Invitrogen, Carlsbad, California.
DNAClean and Concentrator-5 kits are Zymo Research, Orange, California；And
There is sale in QiagenPCR purification kits, market.
Claims (6)
- Prostate cancer diagnosis, research and treatment method, including but not limited to cancer markers 1. a kind of noninvasive high flux methylates, There is provided biological sample of the composition therefor from subject and comprising genomic DNA, it is characterised in that based on big Flux DNA methylation assay combination sequencing M-NGS is identified in the gene related to carcinoma of prostate simultaneously plus the cfRNA information in blood The change to methylate：Detect subject biological sample one or more gene in DNA methylation presence or absence, with produce by The methylome of examination person, including SOBP is established, SUCLG2, SHOX2, the specific C pG islands site that ZDHHC1 genes contain, use Specific anti-methlycytosine antibody identifies and is attached to the DNA fragmentation to methylate, is reached using immunoprecipitate The effect of enrichment, to realize the methylate foundation of two generation sequencing libraries and the enrichment of target site；And methylating subject Compared with spectrum is composed with one or more standard methylations, " waterfall " mechanism is utilized to calculate methylation sites sequencing biological information Whether the comprehensive analysis subject that draws a conclusion has cancer, and cancer is determined with reference to the gene information from acellular ribonucleic acid cfRNA The generation and positioning of disease.
- Prostate cancer diagnosis, research and treatment method 2. noninvasive high flux according to claim 1 methylates, there is provided come from Be diagnosed as the biological sample of the subject of cancer, comprising genomic DNA, it is characterised in that characterize the diagnosis side of qualitative cancer Method, detect methylation level of the gene in the CGI Dao He CpG islands of promoter region, the diagnostic markers as prostate cancer Thing and clinical target, when methylation level increase be present, corresponding is exactly that the expression of the gene reduces；2a. from from by Genomic DNA is extracted in the biological sample of examination person, bisulfite conversion then is carried out to it；2b. detects gene methylation In the 5` non-translational regions of gene, gene SOBP, the SUCLG2 are detected using vitro assay high flux two generations sequenator, SHOX2, ZDHHC1 methylation state, in the given the test agent of the subject, the methylation of said gene relative to Normal prostate cell, instruction result show methylation level it is elevated be prostate cancer.
- Prostate cancer diagnosis, research and treatment method 3. a kind of noninvasive high flux methylates, there is provided from be diagnosed as cancer by The biological sample of examination person, it is characterised in that detect the presence or absence of the biological sample genomic DNA methylation level of subject, use methyl Change sensitive restriction enzyme digested genomic dna, gene magnification then is carried out to the DNA fragment specific containing CpG islands.
- Prostate cancer diagnosis, research and treatment method 4. noninvasive high flux according to claim 1 methylates, its feature exist In diagnostic method algorithm：The change of SOBP, SUCLG2, SHOX2, ZDHHC1 DNA methylation pattern will be calculated with following formula：Diagnose Zong CpG islands in total methylated CpG island/4 gene in the gene of hazards=4Diagnostic method：If this numeral is less than 0.15, patient is just without any prostate cancer risk；If for this numeral between 0.15-0.3, the risk that patient is diagnosed as early-stage cancer is very high；If this numeral is more than 0.3, then the risk that patient is diagnosed as the T2 phases or more is very high.
- Prostate cancer diagnosis, research and treatment method 5. the noninvasive high flux according to claim 1 or 3 methylates, it is special Sign isA.cfRNA information technologies：The RNA discharged using the tumour cell to dissociate in blood, can strongly resist the core in blood The degraded of ribonuclease T., and enough levels be present and be able to carry out quantitative analysis this characteristic, and RNA of these circulations exist It is obvious compared with health in the serum and blood plasma of cancer patient to rise, by the gene information that they are obtained, with reference to subject Methylation profiles result, and then provide definite diagnostic result；B. the methylome of methylome and carcinous sample of the standard methylation spectrum selected from non-cancerous sample；C. it is described provide cancer subject biological sample and comprising genomic DNA, including the tissue of the subject of cancer, Blood, blood plasma, serum, urine, urine supernatant, urine cell precipitation, seminal fluid, prostatic secretion and prostatic cell；D. immunoprecipitation IP buffer solutions contain 100-200mM sodium chloride and 0.02-1.0%Triton X-100 10mM sodium phosphates Buffer solution；E. the reagent for detecting DNA methylation includes the methylation sensitive of genomic DNA of the digestion containing one or more genes Restriction Enzyme, methylation sensitive restriction enzyme include Hin 61 or HpaH.
- Prostate cancer diagnosis, research and treatment method 6. noninvasive high flux according to claim 1 methylates, its feature exist Library is established in compound-two generations sequencing (M-NGS) of the methyl：Methylate the sequencing of two generationsThe genomic DNA that 6a. separates 5 micrograms from LNCaP cells be ultrasonically treated toScope, and use Qiagen PCR purification kits are purified, and 6b. repairs end using the Illumina schemes of standard, by poly A afterbodys and adapter Be added in piece segment DNA, 6c. then by the piece segment DNA in 95 DEG C of thermal denaturations 10 minutes, and quick cooling, 6d. will on ice The anti-methlycytosine antibody of 5 micrograms in DNA and IP buffer solutions is incubated overnight for 4 DEG C in an oscillator, the IP bufferings of immunoprecipitation Liquid contains 140mM sodium chloride and 0.05%Triton X-100 10mM sodium phosphate buffers；6e. by with 100 microlitres of albumin As Resin beads are incubated 2 hours at 4 DEG C, collect methylation fragment；6f. by Protein A resin bead at 4 DEG C in immunoprecipitation IP Wash 4 times, and be resuspended in 200 microlitres of TE buffer solutions containing 0.25%SDS and 5 micrograms of protein enzyme K in buffer solution, and 55 It is incubated 2 hours at DEG C；6g. uses DNA Clean and Concentrator-5 kits samples, according to Illumina ChIP-Seq schemes prepare library；6h. quantifies the library using Bio-Analyzer, and uses each library 10nM concentration Prepare the flow cell per the cluster of swimming lane about 30,000.
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108410969A (en) * | 2018-03-03 | 2018-08-17 | 上海渥恩生物科技有限公司 | Tumor-related gene DNA methylation assay banking process and application |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2009138392A1 (en) * | 2008-05-14 | 2009-11-19 | ETH Zürich | Method for biomarker and drug-target discovery for prostate cancer diagnosis and treatment as well as biomarker assays determined therewith |
| CN103088433A (en) * | 2011-11-02 | 2013-05-08 | 深圳华大基因科技有限公司 | Construction method and application of genome-wide methylation high-throughput sequencing library and |
| CN103103624A (en) * | 2011-11-15 | 2013-05-15 | 深圳华大基因科技有限公司 | Method for establishing high-throughput sequencing library and application thereof |
| CN104024436A (en) * | 2011-10-24 | 2014-09-03 | 纯德赛尔医药公司 | Marker genes for prostate cancer classification |
-
2017
- 2017-07-07 CN CN201710550917.2A patent/CN107460238A/en not_active Withdrawn
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2009138392A1 (en) * | 2008-05-14 | 2009-11-19 | ETH Zürich | Method for biomarker and drug-target discovery for prostate cancer diagnosis and treatment as well as biomarker assays determined therewith |
| CN104024436A (en) * | 2011-10-24 | 2014-09-03 | 纯德赛尔医药公司 | Marker genes for prostate cancer classification |
| CN103088433A (en) * | 2011-11-02 | 2013-05-08 | 深圳华大基因科技有限公司 | Construction method and application of genome-wide methylation high-throughput sequencing library and |
| CN103103624A (en) * | 2011-11-15 | 2013-05-15 | 深圳华大基因科技有限公司 | Method for establishing high-throughput sequencing library and application thereof |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108410969A (en) * | 2018-03-03 | 2018-08-17 | 上海渥恩生物科技有限公司 | Tumor-related gene DNA methylation assay banking process and application |
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Application publication date: 20171212 |