CN110241217A - Early diagnose the molecular labeling of cancer of pancreas - Google Patents
Early diagnose the molecular labeling of cancer of pancreas Download PDFInfo
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- CN110241217A CN110241217A CN201910624688.3A CN201910624688A CN110241217A CN 110241217 A CN110241217 A CN 110241217A CN 201910624688 A CN201910624688 A CN 201910624688A CN 110241217 A CN110241217 A CN 110241217A
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- 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
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/574—Immunoassay; Biospecific binding assay; Materials therefor for cancer
- G01N33/57407—Specifically defined cancers
- G01N33/57438—Specifically defined cancers of liver, pancreas or kidney
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/574—Immunoassay; Biospecific binding assay; Materials therefor for cancer
- G01N33/57484—Immunoassay; Biospecific binding assay; Materials therefor for cancer involving compounds serving as markers for tumor, cancer, neoplasia, e.g. cellular determinants, receptors, heat shock/stress proteins, A-protein, oligosaccharides, metabolites
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- 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
- C12Q2600/00—Oligonucleotides characterized by their use
- C12Q2600/118—Prognosis of disease development
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- 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
- C12Q2600/00—Oligonucleotides characterized by their use
- C12Q2600/158—Expression markers
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2800/00—Detection or diagnosis of diseases
- G01N2800/52—Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis
Abstract
The invention discloses a kind of molecular labeling for diagnosis of pancreatic cancer, which is CENPQ.The present invention filters out the candidate gene of the differential expression in control tissue and Pancreatic Adenocarcinoma by the cancer of pancreas gene expression profile in bioinformatic analysis GEO database, then electronically validating is carried out in GEO database, CENPQ has differences expression in control tissue and Pancreatic Adenocarcinoma as the result is shown, and CENPQ can be used as the molecular labeling of diagnosis of pancreatic cancer.
Description
Technical field
The invention belongs to biomedicine fields, are related to a kind of molecular labeling for early diagnosing cancer of pancreas.
Background technique
Cancer of pancreas (PCA) is that a kind of grade malignancy is very high, all highly difficult malignant tumor of digestive tract of diagnosing and treating, about
90% is the duct adenocarcinoma originating from glandular tube epithelium.This disease disease incidence male is higher than women, and the ratio between men and women is 1.5~2:1, male
Patient is common far beyond premenopausal women, and the disease incidence of postmenopausal women and male are similar.The cause of disease Shang Bushi of cancer of pancreas at present
It distinguishes one from the other.Its occur with smoke, drink, high-fat and high-protein diet, excess coffee for drinking, environmental pollution and inherent cause have
It closes；The disease incidence of cancer of pancreas is apparently higher than general population in survey report discovery diabetic population in recent years；Also someone pays attention to
To chronic pancreatitis patient and cancer of pancreas morbidity there are certain relationship, it is found that the ratio of cancer of pancreas occurs for chronic pancreatitis patient
It is obvious to increase.In recent years, the disease incidence of cancer of pancreas is significantly raised, and since the thirties, American and Britain, Deng state PCA disease incidence increase 2
~4 times.Disease incidence of the Shanghai City PCA in malignant tumour is risen to the 8th in 1993 by the 14th in 1974.PCA hair
The sick increased speed of rate is only second to cancer of pancreas, about increases by 1.5% within every 10 years.
Although the development of abdominal surgery is maked rapid progress in recent years.Many abdomen illness, including tumour, diagnosis is controlled
The horizontal progress with preclinical medicine for the treatment of, the raising of Imaging Technology and the application of molecular diagnostic techniques and greatly mentioned
It is high.But the progress in terms of the diagnosing and treating of cancer of pancreas is unsatisfactory.The concealment of PCA onset, symptom lack specificity, normal companion
There are early stage diffusion and transfer phenomena, is worst one of the malignant tumour of prognosis.85% Patients with Pancreatic Cancer has belonged to advanced stage when medical,
Only 20% or so operable is treated.Annual PCA death and incidence rate are 0.99, and the five year survival rate for making a definite diagnosis patient is
1.3%, Mass median life cycle only 4.1 months, referred to as " the obstinate fort of 21st century medicine ".
The detection of cancer of pancreas at present mainly passes through iconography, tissue biopsy, Serologic detection etc..However, iconography vulnerable to
Operator's experience influences, and depends on equipment, somewhat expensive, especially in the limited situation of medical resource, accuracy rate
It is difficult to ensure, it is difficult to be applied extensively with routine, and CT and ultrasonic wave are difficult to diagnose the pancreatic neoplasm less than 2cm.Organize biopsy
It is the current goldstandard for clinically making a definite diagnosis cancer of pancreas, but there are significant limitations for tissue biopsy, such as the difficulty for sampling of performing the operation, or
The certain cancer location inconvenience of person puncture, and puncture and also bring along certain clinical risk in itself, puncture screening more repeatedly
Great pain can be brought to patient.It is detection to carcinomebryonic antigen (CEA) that Serologic detection is most widely used at present, but CEA pairs
The sensitivity and specificity of Early pancreatic carcinoma are not high, often just increase after tumour shifts.
Therefore, new pancreas carcinoma marker, the especially marker of early warning and monitoring and early diagnosis are found to raising early stage
The diagnosis of cancer of pancreas realizes early intervention treatment, reduces pancreatic cancer mortality and has very important significance.
Summary of the invention
The purpose of the present invention is to provide a kind of molecular labelings for diagnosis of pancreatic cancer.Molecular labeling of the invention can be
The early stage of disease can fast and accurately be diagnosed.
Specifically, present invention employs following technical solutions:
According to an aspect of the present invention, described the present invention provides a kind of molecular labeling for diagnosis of pancreatic cancer
Molecular labeling is CENPQ.
According to the second aspect of the invention, the present invention provides a kind of for detecting the examination of mentioned-above molecular labeling
Agent.
Further, the reagent includes quantitative fluorescent PCR, genetic chip or immunization method detection molecules label expression
Reagent.
Further, the reagent of molecular labeling expression described in the fluorescence quantitative PCR detection includes specific amplified
The primer of CENPQ gene；The reagent of molecular labeling expression described in the genechip detection includes and CENPQ gene recombination
Oligonucleotide probe.
According to the third aspect of the invention we, the present invention provides a kind of for detecting the reagent of mentioned-above molecular labeling
Box, the kit include mentioned-above reagent.
Specifically, the kit of the invention may include element necessary to inverse transcription polymerase chain reaction.RT-
PCR kit includes the primer that a pair of of specificity is directed to CENPQ gene.Each primer is the core that the gene is directed to specificity
The nucleic acid of the sequence of acid sequence, length can be about 7 to 50bp, and more particularly about 10 to 30bp.In addition, the kit may be used also
Comprising specificity for the primer of the nucleic acid sequence of crt gene.In addition, the RT-PCR kit may include testing tube or conjunction
Suitable vessel, reaction buffer (different pH value and magnesium density), deoxynucleotide (dNTP), enzyme (such as Taq polymerase and reversion
Record enzyme), deoxyribonuclease inhibitor, ribonuclease inhibitor, DEPC- water and sterile water.
In addition, kit of the invention may include element necessary to for operating DNA chip.The DNA chip reagent
Box may include with CENPQ gene or cDNA or the substrate being equivalent in conjunction with the oligonucleotides of its segment, and for constructing fluorescence mark
Reactant, reagent and the enzyme of the probe of note.In addition, the substrate may include crt gene or cDNA or the widow for being equivalent to its segment
Nucleotide.
In addition, kit of the invention may include element necessary to for carrying out ELISA.The ELISA kit can
The antibody of CENPQ albumen is directed to comprising specificity.The antibody has the highly selective and affinity for CENPQ albumen, with
Other albumen no cross reactions, and can be monoclonal antibody, polyclonal antibody or recombinant antibodies.In addition, the ELISA
Kit may include the antibody that specificity is directed to reference protein.In addition, the ELISA kit also may include being able to detect to be tied
The reagent of the antibody of conjunction, for example, label secondary antibody, chromophore, enzyme (for example, and antibody conjugate) and its substrate or can tie
Close the substance of the antibody.
According to the fourth aspect of the invention, the present invention provides mentioned-above molecular labeling, mentioned-above reagents to exist
Prepare the application in diagnosis of pancreatic cancer product.
Further, the product includes kit, chip or test paper.
Further, the product realizes diagnostic purpose by CENPQ gene expression in detection sample.
Samples sources of the present invention can be subject or normal person's body fluid middle reaches from DNA fragmentation, or derive from
Complete genome group DNA in organelle, cell and tissue.Wherein, body fluid is blood, urine, sweat, sputum, excrement, brain ridge
Liquid, ascites, hydrothorax, bile, pancreas liquid etc..
According to the fifth aspect of the invention, the present invention provides a kind of diagnostic methods of cancer of pancreas, which comprises
(1) sample of subject is collected；
(2) the CENPQ gene expression amount in the sample of detecting step 1；
(3) compared with sample by normal sample or cancer, the CENPQ gene expression amount that step 2 detects significantly is increased, then should be by
Risk of the examination person with cancer of pancreas or with cancer of pancreas is big.
" compared with sample by normal sample or cancer, the CENPQ gene expression amount that step 2 detects significantly is risen for statement or phrase
It is high " mean as measured by a variety of methods, the CENPQ gene expression dose of subject be normal control 1.0,1.5,2,
3,5,10 or 15 times.
For the present invention, measurement gene expression amount includes measurement gene mRNA content or protein content, wherein measurement
MRNA content refers to the content or combinations thereof for measuring the gene mRNA overall length content or measuring a certain segment on the gene mRNA.
Example for measuring the method for protein content includes, but are not limited to protein chip measurement, immunoassays, ligand
Binding assay, MALDI-TOF (substance assistant laser desorpted/ionization time of flight mass spectrometry), SELDI-TOF (surface-enhanced laser
Desorption/ionization time of flight mass spectrometry), radiommunoassay, radioimmunodiffusion, two-way Immune proliferation (Ouchterlony
Immunodiffusion), rocket immunoelectrophoresis, immunohistochemical staining, complement fixation test (CFT), 2-D electrophoresis, liquid chromatography-mass spectrography
(LC-MS), liquid chromatography-mass spectrography/mass spectrum (LC-MS/MS), immunoblotting and ELISA (enzyme-linked immunosorbent assay).
Reagent for measuring protein content may include the antibody that can be specifically bound to albumen, oligopeptides, ligand, PNA (peptide
Nucleic acid) or aptamer.
The term as used herein " antibody " refers to molecule of the antigen binding to cause the substance of antigen-antibody reaction.For
The purpose of present disclosure, term " antibody " mean the antibody for being specifically bound to albumen.Fall into the antibody model of present disclosure
What is enclosed is polyclonal antibody, monoclonal antibody and recombinant antibodies.Technology well known in the art can be used easily to make for these antibody
?.For example, as known in the art, it can obtain by injecting the CENPQ albumen for being used as antigen in animal and from the animal
It obtains serum antibody-containing and prepares polyclonal antibody.Polyclonal antibody can be used any animal (for example, goat, rabbit, sheep,
Monkey, horse, pig, ox, dog etc.) and be made.Monoclonal antibody can pass through hybridoma method (Kohler and Milstein (1976)
European Journal ofImmunology 6:511-519) or phage antibody library technique (Clackson et al.,
Nature, 352:624-628,1991；Marks et al., J.Mol.Biol., 222:58,1-597,1991) it obtains.The antibody
Gel electrophoresis, dialysis, salt precipitating, ion-exchange chromatography, affinity chromatography etc. can be used to be separated and purified.In addition, being applicable in
It can be the complete antibody being made of two full-length light chains and two total length heavy chains in the antibody of present disclosure, or complete anti-
The function fragment of body molecule." function fragment " of term antibody molecule means the segment for retaining antibody binding function, such as Fab, F
(ab '), F (ab ') 2 and Fv.
Term " PNA (peptide nucleic acid) " as used herein refers to artificial synthesized polymer similar with DNA or RNA,
It is firstly introduced by Nielsen, Egholm, Berg and Buchardt (University Copenhagen Denmark) professor within 1991.DNA has phosphorus
Acid-ribose backbone, and the skeleton of PNA is made of duplicate N- (2- the amino-ethyl)-glycine unit being keyed by peptide.By
In this structure, PNA significantly increases the binding affinity and stability of DNA or RNA, therefore is efficiently used for molecular biology and grinds
Study carefully, diagnose and antisense therapy.Detailed description for PNA, can refer to document [Nielsen PE, Egholm M, Berg RH,
Buchardt O (in December, 1991) " Sequence-selective recognition of DNA by
Stranddisplacement with a thymine-substituted polyamide " .Science 254 (5037):
1497-1500]。
" aptamer " used herein is the oligonucleotides or peptide molecule for being bound to certain target molecules.Specifically for aptamer
It is bright, it can refer to document [Bock LC et al., Nature 355 (6360): 5646 (1992)；Hoppe-Seyler F, Butz K "
Peptide aptamers:powerful new tools for molecular medicine " .J Mol Med.78 (8):
42630(2000)；Cohen BA, Colas P, Brent R. " An artificial cell-cycle
inhibitorisolated from a combinatorial library″.Proc Natl Acad Sci USA.95
(24): 142727 (1998)].
The term as used herein " measurement mRNA content " means the presence of the mRNA of CENPQ gene in detection and identification sample
And expression.
In this disclosure, the example that can be used for measuring the analysis method of mRNA expression includes reverse transcription polymerase
Chain reaction (RT-PCR), competitive RT-PCR, real-time RT-PCR, ribonuclease protection assay (RPA), RNA blotting and
DNA chip, but not limited to this.
Reagent for measuring mrna expression include the primer specifically bound with the mRNA of gene, probe or
GEM 132.Those skilled in the art can be specifically bound based on the mRNA of the gene of the information design and encoding said proteins
Primer, probe or GEM 132.
Term " primer " as used herein is the chain for identifying the short nucleic acid sequences of target-gene sequence comprising a pair of positive and negative
To primer.Specifically, described " primer " it include the specific primer with the analysis result of sensitivity of a pair of of offer.Primer is considered
For providing high degree of specificity when expanding target-gene sequence, but do not cause and inconsistent or not complementary non-of target-gene sequence
The amplification of target sequence.
The term as used herein " probe " refers to the substance for being specifically bound to target to be detected in sample.By described
In conjunction with probe can determine the presence of target in sample.As long as it is commonly used in this field, any probe is used equally for the disclosure
Content.Particularly, the probe can be PNA (peptide nucleic acid), LNA (lock nucleic acid), peptide, polypeptide, protein, RNA or DNA, most
It is preferred that PNA.Specifically, the probe is to may be from biology or the biomaterial that can in vitro synthesize or its analogies.Example
Such as, the probe can be enzyme, albumen, antibody, microorganism, animal or plant cell or organ, neuron, DNA or RNA.Institute
Stating DNA may include cDNA, genomic DNA and oligonucleotides.Geneome RNA, mRNA and oligonucleotides can also fall into the RNA's
In range.The example of the albumen includes antibody, antigen, enzyme and peptide.
The term as used herein " antisense oligomers " refers to nucleotide base sequence and subunit-subunit backbone oligomerization
Body, the skeleton allows antisense oligomers to hybridize by Watson-Crick base pairing with the target sequence in RNA, described
RNA is formed in target sequence: oligomer heteroduplex.The oligomer can have accurate or close with the target sequence
Complementarity.
According to the present invention, after measuring CENPQ gene expression amount, use in normal sample CENPQ gene content as ginseng
According to by CENPQ gene content corresponding in subject's sample standardization.For example, same in normal sample and subject's sample
One gene content is respectively X and Y, then the gene content is Y/X in subject's sample.
Compared with prior art, the method that the present invention detects cancer of pancreas is to be based on CENPQ gene expression amount, therefore can make
With more extensive DNA sample source.Therefore, the method that the present invention detects cancer of pancreas has several advantages that (1) DNA comes
Source is extensive, and there is no the check frequencies in iconography；(2) accuracy is high, has higher sensitivity and special to Early pancreatic carcinoma
Property, the early screening suitable for cancer of pancreas.Gene marker of the invention can be combined with other clinical indices, be cancer of pancreas
Screening, diagnosis, treatment and prognosis provide more accurately judgement.
The term as used herein " cancer of pancreas " means the cancer (cancer) or malignant tumour that the cell in pancreas generates.There are many
The pancreatic neoplasm of type, the malignant tumour excessively poor to prognosis from the benign tumour that can be cured by operation excision.It is benign swollen
Tumor, malignant tumour and it is transformed into the benign tumour of malignant tumour and is included in the range of pancreatic neoplasm.As for the evil of pancreas
Property tumour, the 90% of this kind of tumour is ductal adenocarcinoma of pancreas (PDAC).Therefore, ductal adenocarcinoma of pancreas is in a narrow sense referred to as pancreas
Cancer.Other examples of cancer of pancreas include neuroendocrine tumor and acinar cell tumor.In addition, pancreatic neoplasm can be cystoma
Form, it is such as false by serosity cystoma, mucinous cystic tumors, pancreatic intraductal papillary mucus tumour (IPMN) and solid
Papilloma typically indicates.
Specifically, cancer of pancreas can be ductal adenocarcinoma of pancreas or IPMN.Ductal adenocarcinoma of pancreas can produce due to various reasons
It is raw.For example, ductal adenocarcinoma of pancreas may derived from IPMN or may be unrelated with IPMN and generate.Alternatively, ductal adenocarcinoma of pancreas
It can exclude ductal adenocarcinoma of pancreas derived from IPMN.According to the staging of WHO, IPMN be defined as epithelial cell in main pancreatic duct or
Tumour (knob) made of being grown in the form of mamillary in its branch's ductus pancreaticus, it is characterised in that tumour cell generates thick liquid
And tumour is diffused to from ductus pancreaticus.
In addition, it includes the diagnostic reagents of cancer of pancreas the present invention provides the kit for diagnosis of pancreatic cancer.Specifically
Ground, the kit can for RT-PCR kit, DNA chip kit, ELISA kit, protein chip kit, quickly
Kit or MRM (multiple-reaction monitoring) kit.
The term as used herein " diagnosis " be intended to cover to determine subject to the neurological susceptibility of certain disease or illness, determine by
Prognosis (such as the identification cancer whether examination person suffers from certain disease or illness, determines the subject with certain disease or illness
Transfer before state or transfering state, the response to treatment of stage or cancer that determines cancer) or treatment measurement
(therametrics) (for example, the state of monitoring subject is to provide the information about therapeutic efficiency).Specifically, used herein
Diagnosis mean determine cancer of pancreas morbidity or morbidity a possibility that (risk).
The term as used herein " molecular labeling " means to allow to distinguish normal and morbid state or can make treatment results quilt
The label of prediction or objective measurement.Specifically, in context relevant to cancer of pancreas, molecular labeling mean suffer from cancer of pancreas or
Have in the subject of risk of pancreatic cancer, compared to normal control (subject for being not suffering from cancer of pancreas), albumen or gene table
The organic biomolecules being significantly raised and lowered up to level, such as polypeptide or nucleic acid (such as mRNA etc.), lipid, glycolipid, sugared egg
White, sugared (monosaccharide, disaccharides, oligosaccharides etc.) etc..
Term " subject " used herein refers to the subject that pending cancer of pancreas morbidity checks comprising cancer of pancreas
Patient, doubtful subject with cancer of pancreas and the normal subjects for being not suffering from cancer of pancreas.For example, the inspection of PDAC medicine will be carried out
It looks into, make a definite diagnosis the health volunteer of history without clinical cancer of pancreas, or although cut off tumour, periodically examined due to cancer of pancreas passing medical history
The subject looked into falls into the range of the subject.In one embodiment, the subject can be mammal, and
It can be the mankind in another embodiment.
Detailed description of the invention
Fig. 1 shows the statistical chart of CENPQ expression conditions；
Fig. 2 is the ROC curve figure of molecular labeling differentiating pancreatic cancer patient and Healthy People of the invention.
Specific embodiment
Below with reference to examples and drawings, the present invention is described in detail, so that those skilled in the art better understand
The present invention, and can be practiced.
Embodiment 1 screens gene relevant to cancer of pancreas
1, NCBI GEO (Gene Expression Omnibus) data retrieval
GEO (Gene Expression Omnibus) database is by NCBI (US National Biotechnology Information center)
Exploitation maintenance, database of the GEO database as maximum gene expression data, the database is based on chip data, furthermore
Also (ribosomes sequence label connects by data such as SAGE (serial analysis of gene expression) data comprising some non-chip types, SARST
Continuous analysis) (MPSS is surveyed in parallel on a large scale for data, MS (mass spectrum) data, proteome data and high-flux sequence data of new generation
Sequence technology) etc..
Search key: (pancreatic cancer) AND " Homo sapiens " [porgn] AND (" gse "
[Filter])
Be included in standard: 1. studying type is " expression profiling by array "；2. data are from pancreas
Cancerous swelling tumor tissue and control group (normal pancreatic tissue or Pancreas cancer patients cancer beside organism)
(3) 10 sets of cancer of pancreas mRNA expression chip data sets
The basic condition of 1 10 sets of data collection of table
2, data analysis step
(1) Differential expression analysis
After transcript profile Data Analysis Software carries out background correction and standardization to initial data, metaMA in R language is utilized
Wrap (document G.Marot, J.-L.Foulley, C.-D.Mayer and F.Jaffrezic (2009) Moderated
effect size and P-value combinations for microarray meta-
Analyses.Bioinformatics 25 (20): 2692-2699.) data analysis is carried out, merging effect value, (English can state
For Calculates effect sizes from unpaired data either from classical or
moderated t-tests(Limma,SMVar)for each study and combines these effect
Sizes.), difference expression gene 974 are obtained, 428 difference expression genes raise in Pancreas cancer patients tumor tissues, and 546
A gene lowered in Pancreas cancer patients tumor tissues (screening criteria are as follows: FDR<0.05, | diff |>0.5).Note: | diff |
After meaning the average value of average value-control of case, take absolute value.
(2) GO enrichment analysis and the analysis of KEGG signal path
It the use of software is genecordis, network address is http://genecodis.cnb.csic.es/, is enriched with Analysis and Screening
Standard is FDR < 0.05.GO function is enriched with the results show that 974 gene significant enrichments are in endocrine pancreas development (endocrine
Pancreas development), the adjusting (regulation of insulin secretion) of insulin secretion, pancreas islet
Plain receptor signaling pathways (insulin receptor signaling pathway), vascular system develop (vasculature
The bioprocess such as development) are related to insulin-like growth factor and combine (insulin-like growth factor
Binding), insulin-like growth factor activated receptor activity (insulin-like growth factor-activated
Receptor activity) etc. molecular functions.KEGG access enrichment the results show that 974 difference expression gene significant enrichments
In pancreatic secretion (Pancreatic secretion), cancer of pancreas (Pancreatic cancer), cancer approach (Pathways
In cancer), the signal paths such as insulin signaling pathway (Insulin signaling pathway).
The gene C ENPQ that there may be diagnostic significance is selected according to the result of embodiment 1, in GEO database further
Verifying.
The verifying of 2 difference expression gene of embodiment
1, data collection
It is selected differently from the new data set of embodiment 1 from GEO database, collects Pancreatic Adenocarcinoma and corresponding cancer altogether
79, side tissue.
2, data are analyzed
Expression of the CENPQ gene in Pancreatic Adenocarcinoma and cancer beside organism is analyzed, column diagram is drawn.Use R language
In pROC packet analysis CENPQ gene Receiver Operating Characteristics, calculate the accurate confidence space of binomial, draw ROC curve.
3, result
As a result as shown in Figure 1, compared with cancer beside organism, CENPQ gene expression is significantly raised in Pancreatic Adenocarcinoma, difference tool
Statistically significant (P < 0.05).Fig. 2 shows that the AUC value of ROC curve is 0.821.
Finally it should be noted that the above content is merely illustrative of the technical solution of the present invention, rather than the present invention is protected
The limitation of range, the simple modification or equivalent replacement that those skilled in the art carry out technical solution of the present invention,
All without departing from the spirit and scope of technical solution of the present invention.
Claims (10)
1. being used for the molecular labeling of diagnosis of pancreatic cancer, which is characterized in that the molecular labeling is CENPQ.
2. the reagent for detecting molecular labeling described in claim 1.
3. reagent according to claim 2, which is characterized in that the reagent includes quantitative fluorescent PCR, genetic chip or exempts from
The reagent of epidemic disease method detection label expression.
4. reagent according to claim 2, which is characterized in that the expression of molecular labeling described in the fluorescence quantitative PCR detection
Horizontal reagent includes the primer of specific amplified CENPQ gene；Molecular labeling expression described in the genechip detection
Reagent includes the oligonucleotide probe with CENPQ gene recombination.
5. the kit for detecting molecular labeling described in claim 1, which is characterized in that the kit includes that right is wanted
Seek reagent described in any one of 2-4.
6. reagent described in any one of molecular labeling described in claim 1, claim 2-4 is produced in preparation diagnosis of pancreatic cancer
Application in product.
7. application according to claim 6, which is characterized in that the product includes kit, chip or test paper.
8. application according to claim 6 or 7, which is characterized in that the product passes through CENPQ gene table in detection sample
It reaches to realize diagnostic purpose.
9. application according to claim 8, which is characterized in that the samples sources are biological tissues.
10. a kind of diagnostic method of cancer of pancreas, which is characterized in that the described method includes:
(1) sample of subject is collected；
(2) the CENPQ gene expression amount in the sample of detecting step 1；
(3) compared with sample by normal sample or cancer, the CENPQ gene expression amount that step 2 detects significantly is increased, then the subject
With cancer of pancreas.
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
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| WO2012031122A2 (en) * | 2010-09-03 | 2012-03-08 | Immport Therapeutics, Inc. | Methods and compositions for the diagnosis and treatment of cancer and autoimmune disorders |
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