CN107619863A - Method for detecting the Presence of a cancer - Google Patents
Method for detecting the Presence of a cancer Download PDFInfo
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Abstract
The invention provides a method for detecting the existing risk of cancer, which comprises providing a blood sample of an individual and a non-cancer control group, measuring the expression level of cancer gene markers, calculating the basic expression level of individual genes of the non-cancer control group, and dividing the individual gene expression level of the individual and the non-cancer control group by the basic expression level of the individual genes to calculate the expression magnification of each gene; taking the natural logarithm of the multiplying power to ensure that the rising times or the falling times have the same weight; the final natural log addition factor is the cancer risk index, which is used to assess the risk of a cancer and the response and prognosis of a patient after cancer treatment.
Description
Technical field
The present invention is on a kind of method for the presence risk for detecting cancer；It is particularly a kind of to utilize 18 cancer gene marks
The method of the presence risk of note detection cancer.
Background technology
In recent years, molecular medicine science and technology is gradually developed for the risk of cancer diagnosis of blood sample and the cancer base of prediction
Because of mark, those marks can be used for early detection to improve the survival rate of patient, be included in symptom for before clinically can detect,
When receiving treatment and when restoring.The big more options of those technologies and cancer related gene group, observe cancer patient and common people
Difference on this genome, generally utilize Pearson correlation coefficient (Pearson's correlation
Coefficient probability transformation mechanism or judgment mechanism) are established, then the gene performance of subject is imported into foregoing probability interpreter
System or judgment mechanism are tested.
However, the above method only transmits Pearson correlation coefficient, it is a kind of linearly dependent coefficient, for reflecting two
The statistic of linear variable displacement degree of correlation.This method has following shortcoming：(1) this method need to consider those gene performance figures
Whether shape (pattern) similar, easily occur judging by accident in gene performance all normal fluctuation range but gene performance figure it is close,
And do not consider whether gene performance amount height is reasonable；(2) this method is consideration term single gene table line distribution situation in colony
And ignore interindividual variation；And (3) term single gene effect deficiency.
Therefore, the cancer gene currently used for risk of cancer diagnosis and the prediction of blood sample marks, and lacks a kind of use
The gene performance amount of colony is as basic value to reduce individual influence, and the method being weighted to gene.
The content of the invention
In view of this, the present invention provides a kind of method for the presence risk for detecting cancer, and its step includes：(a) from one by
Examination person obtains the corpse or other object for laboratory examination and chemical testing sample of the body fluid comprising nucleic acid；(b) mrna expression amount of a cancer gene mark group, the cancer are measured
Genetic marker group be by betaglobulin (hemoglobin beta gene, HBB), glycosylated hemoglobin (hemoglobin A1,
HBA1), cytohormone message mortifier -3 (suppressor of cytokine signalling 3, SOCS3), adrenal gland
Medullarin (adrenomedullin, ADM), secreting type Leucoprotease suppress albumen (secretory leukocyte
Protease inhibitor-1, SLP1), surface antigen differentiation cluster 68 (cluster of differentiation 68,
CD68), S100 calbindins P (S100calcium binding protein P, S100P), DNA damage induction transfer because
3 (DNA damage inducible transcript 3, DDIT3) of son, Ctsz (cathepsin Z, CTSZ),
Bcl-2 correlations X protein (Bcl-2-associated protein x, Bax), amyloid precursor albumen (amyloid
Precursor protein, APP), turn keto-alcohol ferment enzyme (transketolase, TKT), G-protein coupling ERs (G
Protein-coupled estrogen receptor, GPER), Hemopexin and Hemopexin it is related
Albumen (haptoglobin and haptoglobin-related, HPR | HP), (FK506Binding of FKBPL 3
Protein3, FKBP3), acid phosphatase 5 (acid phosphatase 5, ACP5), lysosome related protein cross-film 4alpha
(lysosomal protein transmembrane 4alpha, LAPTM4A) and Chemokine receptor4 (chemokine
Receptor, CXCR4) formed；(c) the risk of cancer index of the subject is calculated, its formula is sum [LN (Individual genes tables
The now basal expression amount of amount/Individual genes)], comprising：(i) basal expression of Individual genes performance amount divided by an Individual genes is taken
Measure to calculate the expression multiplying power of each gene；(ii) again by multiplying power take natural logrithm make rising multiple or decline multiple have it is identical
Weight；(iii) gene expression amount ascensionist confirms the presence risk for having cancer, and gene expression amount descender does not consider；With
And (iv) adds up the risk of cancer index that the genes of individuals expression affiliated weight of ascensionist is subject；(d) Individual genes
Basal expression amount is taken from the expression of the corresponding cancer gene of the corpse or other object for laboratory examination and chemical testing sample of the body fluid containing nucleic acid of a non-cancer control group
The geometric mean of amount；And (e) calculates the risk of cancer index of non-cancer control group with step (c)；It is wherein tested based on this
The risk of cancer index of person is to represent the subject to have less than the median person of the risk of cancer index of the non-cancer control group
Form the low-risk of cancer；Risk of cancer index based on the subject is higher than the risk of cancer index of the non-cancer control group
99% credibility interval (C.I.) person, representing the subject has the excessive risk for forming cancer.
The present invention separately provides a kind of method of one patient of assessment to the prognosis recurrence risk for the treatment of of cancer, and its step includes：
(a) corpse or other object for laboratory examination and chemical testing sample of the body fluid comprising nucleic acid is obtained from a subject；(b) the mRNA expression of a cancer gene mark group is measured
Amount, the cancer gene mark group be by HBB, HBA1, SOCS3, ADM, SLPl, CD68, S100P, DDIT4, CTSZ, BAX, APP,
TKT, GPER, HPR | HP, FKBP3, ACP5, LAPTM4A and CXCR4 are formed；(c) risk of cancer for calculating the subject refers to
Number, its formula are sum [LN (basis of Individual genes performance amount/Individual genes reaches amount)], comprising：(i) Individual genes are taken to express
Amount divided by the basal expression amount of an Individual genes are to calculate the expression multiplying power of each gene；(ii) multiplying power is taken into natural logrithm again
Rising multiple or decline multiple is set to have identical weight；(iii) gene expression amount ascensionist confirms the presence risk for having cancer, base
Because of expression quantity, descender does not consider；And weight belonging to (iv) totalling individual is the risk of cancer index of subject；(d) should
The basal expression amount of Individual genes is to be derived from the corresponding cancer of the corpse or other object for laboratory examination and chemical testing sample of the body fluid containing nucleic acid of a non-cancer control group
The geometric mean of the expression quantity of disease gene；And (e) calculates the risk of cancer index of non-cancer control group with step (c)；Its
In the risk of cancer index based on the patient less than the non-cancer control group risk of cancer index median person, be represent should
Patient has the low-risk of cancer return；Risk of cancer index based on the patient is higher than the risk of cancer of the non-cancer control group
The credibility interval of index 99% (C.I.) person, representing the patient has the excessive risk of cancer return；And the people of the non-cancer control group
Number need to be more than 20 people.
In one embodiment of this invention, wherein step (b) is via micro- array chip, real time aggregation enzyme chain reaction
(real-time PCR), Northern blot hybridizations or in situ hybridization measure.
In one embodiment of this invention, wherein the cancer is breast cancer, stomach cancer, carcinoma of urinary bladder or liver cancer.
In one embodiment of this invention, wherein the corpse or other object for laboratory examination and chemical testing sample is a PMBC (Peripheral
Blood mononuclear cell, PBMC) sample.
Therefore, the present invention provide it is a kind of detect cancer presence risk method, this method include provide one individual and
The blood sample of non-cancer control group, and the expression quantity of 18 cancer gene marks is measured, wherein 18 cancer genes mark
Comprising by HBB, HBA1, SOCS3, ADM, SLPl, CD68, S100P, DDIT4, CTSZ, BAX, APP, TKT, GPER, HPR | HP,
The group that FKBP3, ACP5, LAPTM4A and CXCR4 are formed, first with the basis for calculating non-cancer control group Individual genes
Expression quantity, then respectively by the basal expression of the Individual genes expression quantity of the individual and non-cancer control group divided by the Individual genes
Measure to calculate the expression multiplying power of each gene；Natural logrithm is taken rising multiple or decline multiple is had identical power multiplying power
Weight；The multiplying power for finally adding up natural logrithm is risk of cancer index, and the risk of cancer index is assessing an individual cancer
The reaction and prognosis situation of risk and a patient after treatment of cancer is received be present.
Embodiments of the present invention described further below, it is set forth below for embodiment be to illustrate the present invention,
The scope of the present invention is not limited to, it is any to be familiar with this those skilled in the art, without departing from the spirit and scope of the present invention, when can do
A little change and retouching, therefore protection scope of the present invention ought be defined depending on appended claims institute defender.
Brief description of the drawings
Fig. 1 is the risk of cancer index number of the single individual single detection of the method for the presence risk of the detection cancer of the present invention
According to figure；
2 figures are that the risk of cancer index that the method patients with gastric cancer of the presence risk of the detection cancer of the present invention continuously detects is bent
Line chart；
Fig. 3 is the cancer wind of the method validation liver cancer for the presence risk that the detection cancer of the present invention is carried out using other chips
Dangerous exponent data figure.
Embodiment
The present invention provides a kind of method for the presence risk for detecting cancer, and this method includes providing an individual and non-cancer
The blood sample of control group, and the expression of 18 cancer gene marks is measured, using the gene expression amount of colony as basic value
Individual influences and the method that is weighted to gene calculates the dangerous index of cancer point to reduce, and the risk of cancer index is assessing
Reaction and prognosis situation of the presence risk and a patient of one individual cancer after treatment of cancer is received.
Definition
Term " genetic marker " used herein, refer to that one kind changes in mRNA performance amounts, and can guide out specific
The increase of the risk of disease or exception.
Term " gene expression amount " used herein, refer to protein or functional r NA products as caused by gene.
Term " non-cancer control group " used herein, refers to that the individual is confirmed and does not suffer from cancer.
Term " micro- array chip " used herein, refers to the micro- array chip that can detect gene expression amount, it can be
AFFYMETRIX, ILLUMINA, AGILENT and micro- array chip of Phalanx Biotech Group Inc., but be not limited to
This.
The method of the presence risk of the detection cancer of the present invention of embodiment 1
The present invention is given by different genes in the expression quantity difference of PMBC (PBMC) to be weighted, and reaches non-cancer
The purpose of disease control group and cancer component group.
Collect genome
First, the border that present invention research cancer occurs has special expression (to over-express or too low in PMBC
Expression) gene；And those genes are observed in detection instrument (the micro- array chips of mRNA or real time aggregation enzyme chain reaction (real-
Time PCR) system or other mRNA analysis methods) expression section, dropped if gene expression amount falls within non-linear reconnaissance range
Low weight (30%, 40%, 50%, 60%, 70% or other can obtain the ratio of preferable analysis result), preferably reduces power
Weigh 50%.
Of the invention 18 and the genetic marker of cancer most correlation, wherein comprising by betaglobulin (hemoglobin
Beta gene, HBB), glycosylated hemoglobin (hemoglobin A1, HBA1), cytohormone message mortifier -3
(suppressor of cytokine signalling 3, SOCS3), adrenomedulin (adrenomedullin, ADM),
Secreting type Leucoprotease suppresses albumen (secretory leukocyte protease inhibitor-1, SLP1), table
Face antigen differentiation cluster 68 (cluster of differentiation 68, CD68), S100 calbindins P
(S100calcium binding protein P, S100P), DNA damage induction transfer factor 3 (DNA damage
Inducible transcript 3, DDIT3), Ctsz (cathepsin Z, CTSZ), Bcl-2 correlation X proteins
(Bcl-2-associated protein x, Bax), amyloid precursor albumen (amyloid precursor
Protein, APP), turn keto-alcohol ferment enzyme (transketolase, TKT), G-protein coupling ERs (G protein-
Coupled estrogen receptor, GPER), Hemopexin and Hemopexin GAP-associated protein GAP
(haptoglobin and haptoglobin-related, HPR | the HP), (FK506Binding of FKBPL 3
Protein 3, FKBP3), acid phosphatase 5 (acid phosphatase 5, ACP5), lysosome related protein cross-film
4alpha (lysosomal protein transmembrane 4alpha, LAPTM4A) and Chemokine receptor4
The group that (chemokine receptor, CXCR4) is formed.
1.2 calculate the rudimentary representation amount of Individual genes
Term single gene does geometric mean (or for table in the expression quantity of Different Individual in the negated cancer control group of the present invention
It is weighted up to amount distribution average) basal expression amount with this as gene.
1.3 calculate the risk of cancer index of individual
Single individual ownership gene in all samples respectively divided by Individual genes basal expression amount, can be obtained gene by the present invention
The multiplying power of expression, natural logrithm is taken rising multiplying power or decline multiplying power is had identical weight multiplying power；Inspect the base for rising multiplying power
Cause, it is the individual risk of cancer index finally to add up the gene weights that gene expression belonging to individual rises.
1.4 carry out a point group
The present invention distinguishes the risk of cancer exponential distribution of the risk of cancer exponential distribution of non-cancer control group and cancer group
Calculate.
Single individual single detection：The individual risk of cancer index is in non-cancer control group normal distribution region median
(or average) is cancer low-risk person below, more than the non-confidence section (C.I.) of cancer control group normal distribution region 99%
Person is cancer excessive risk person, is between the two moderate risk of cancer person.
The single continuous detection of individual：The individual risk of cancer index continuous (2,3,4 or more number) comes across non-cancer
Disease control group normal distribution region or cancer patient distributed areas, then it is corresponding performance (corresponding
performance)。
The checking of the method for the presence risk of the detection cancer of the present invention of embodiment 2
The present invention can accurately be applied to detection, diagnosis cancer and assess treatment of cancer imitate for 18 genetic markers of confirmation
Fruit and the prediction of prognosis, utilize the blood sample of cancer patient and the control group of non-cancer patient 18 genetic markers of measurement
Expression quantity calculates the risk of cancer index of indivedual samples again.
2.1 research samples
Control group sample：The present invention collects 26 PMBCs for not suffering from cancered normal individual after diagnosing
(Peripheral blood mononuclear cell, PBMC) sample, it all obtains agreeing in person for donations sample.Each
Sample at least detects at least twice, and the present invention carries out 55 person-times of testing result altogether.
Cancer sample：The present invention collects the peripheral blood list of a patients with gastric cancer, two bladder cancer patients, patients with mastocarcinoma
Nucleus (PBMC) sample, those patients respectively at before cancer return is made a definite diagnosis, cancer return make a definite diagnosis, treat during or treatment it is laggard
Row detection, it all obtains agreeing in person for donations sample.
2.2RNA extraction
The present invention utilizes according to commodity operation handbookReagent (INVITROGEN companies, the U.S.) extracts RNA,
With super prestige amount light splitting luminance meter (Nano Drop spectrophotometer) (THERMO FISHER after extraction
SCIENTIFIC companies, the U.S.) measurement RNA concentration and purity, by OD260/OD280 ratio and OD260/OD230
Ratio estimation RNA purity, wherein OD260/OD280 ratio is between 1.8 to 2.0；OD260/OD230 ratio is not
The purity that RNA is represented less than 2.0 is good；And commented by micro-fluidic electrophoresis analyzer (model 2100, AGILENT companies, the U.S.)
Estimate RNA clip size, quantification and qualification.
Mankind's chip of expression spectrum (Human Oligonucleotide DNA microarray, HOA) is analyzed
The present invention includes 32 using mankind's chip of expression spectrum v6 (Phalanx Biotech Group Inc., TaiWan, China),
679 probes, each probe are designed as mankind's express spectra gene probe of 60 base oligonucleotides (sense-strand) of long-chain；
Wherein 32,741 probes are the annotation genes with reference to internationally recognized RefSeq and Ensembl sequence libraries, are also wrapped in addition
Containing 938 control group probes.
Chip analysis
Use of the invention uses via 1 μ g RNAAmination mark aRNA amplifing reagents (Hua Lian biology section
Skill limited company, TaiWan, China) and Cy5 stains (unusual medical device corporations, the U.S.) prepare the anti-stock of fluorescence labeling
RNA (aRNA) subject matter.Using crossing system (Phalanx Biotech Group Inc., TaiWan, China) with hybridization buffer
Anti- stock RNA (aRNA) subject matter of the fluorescence labeling is hybridized to this by (Phalanx Biotech Group Inc., TaiWan, China)
On mankind's chip of expression spectrum.After hybridization 16 hours, after the subject matter of non-specific combination is rinsed, scanned using DNA chip
Instrument (model G2565CA, AGILENT companies, the U.S.) carries out chip scanning, and utilizes the software analysis of GenePix 4.1
(Molecular Device companies) analyzes Cy5 fluorescent signal intensity.
Each single sample is at least detected twice makes repeated (reproducibility) more than 0.975, by gained
Signal strength input to Rosetta resolvers system (Rosetta biosoftwares company, the U.S.) with carry out data processing and
By data normalization with 75 hundredths suitable for median.Error weight method (error- is utilized in same time
Weighted approach) assess sample mistake.The expression quantity of paired samples changes and the comparison of both p values is via assessment
Gene differential expression (differentially expressed gene) analysis calculates, and determining the standard of gene differential expression is
Huo≤- 2 of expression quantity Gai Bian≤2 and p value<0.05 with further analysis after progress.
2.5 risk of cancer index analysis
The present invention captures 18 gene expression values in non-cancer control group, takes Individual genes in the geometric average of experiment group
Number is as basal expression amount；It is single by (non-cancer control group and cancer group is included) in all samples as shown in table one and table two
Individual ownership gene difference divided by Individual genes basal expression amount, can obtain the multiplying power of gene expression, take natural logrithm to make multiplying power
Rising multiplying power or declining multiplying power has identical weight, and finally weight belonging to totalling individual is the individual risk of cancer index.
At non-cancer control group normal distribution region confidence section 99% (i.e. risk of cancer index 6.25), above person is cancer
Disease excessive risk person or cancer patient；Risk of cancer index is cancer low-risk person for 3 (median) following persons；Between both (3
And 6.25) between be moderate risk person.In cancerous tissue risk of cancer index：A. cancer wind before a patients with gastric cancer recurrence is made a definite diagnosis
Dangerous index is 8.52,6.08,8.75,18.09 and 10.58, and risk of cancer index is 12.77 before its chemotherapy, cancer during chemotherapy
Disease risk index is 7.90,6.48,6.31,5.27 and 8.45；B. two bladder cancer patients continuously detect risk of cancer index
Respectively 11.63 and 13.31,10.24 and 12.30；C. risk of cancer index is during a patients with mastocarcinoma treatment
11.88, treatment end after one month risk of cancer index be 2.40.Sample above Check-Out Time interval 2 weeks to 8 weeks.
The risk of cancer index of the control group sample of table one
The risk of cancer index of the cancer sample of table two
The single individual single testing result of method of the presence risk of the detection cancer of the present invention, as shown in figure 1, breast cancer,
Stomach cancer, bladder cancer patients obtain optimum detection performance using 18 genetic markers of the present invention, and its efficiency index is：88.2%
Sensitiveness (sensitivity), 91% selectivity (specificity), 90.4% accuracy (accuracy).
The risk of cancer index results that the method patients with gastric cancer of the presence risk of the detection cancer of the present invention continuously detects, such as
Shown in Fig. 2, patients with gastric cancer gradually increases before recurrence is made a definite diagnosis to the risk of cancer index before chemotherapy with the time, to meter during chemotherapy
Calculation machine tomoscan shows that the stable risk of cancer index of cancerous state gradually decreases with the time, it was demonstrated that cancer patient utilizes this hair
18 bright genetic markers can be used for detection cancer to there is and assess prognosis reaction of the patient to treatment of cancer.
Embodiment 3 carries out the checking of the method for the presence risk of the detection cancer of the present invention using other chips
The mrna expression amount that the present invention measures 18 cancer gene mark groups for checking different experiments mode all may be used
Using the method for the present invention.
First, the present invention is via Shi M, Chen MS, Sekar K, Tan CK et al.A blood-based
three-gene signature for the non-invasive detection of early human
hepatocellular carcinoma.Eur J Cancer 2014Mar；50(5):Disclosed in 928-36 papers
All gene expression amounts of Affymetrix Human Genome U133Plus 2.0Array genetic chips, obtain the present invention
The mRNA performance amounts of 18 described cancer genes, the risk of cancer index of the present invention is carried out using the method described in embodiment 2
Analysis.
Risk of cancer exponential distribution is as shown in figure 3, wherein include 10 control group samples (as shown in Table 3), 10 liver cancer
Sample (as shown in Table 4), non-cancer control group normal distribution region confidence section 99% (i.e. risk of cancer index 2.9) with
Upper person is cancer excessive risk person or cancer patient；Risk of cancer index is cancer low-risk person for 1.0 (median) following persons；
It is moderate risk person between both (1 and 2.9).Its efficiency index is：100% sensitiveness (sensitivity), 60%
Selectivity (specificity), 80% accuracy (accuracy).Different experiments can should be utilized by confirming the method for the present invention
The mRNA performances amount that mode is obtained carries out the detection that various cancers have risk.
The risk of cancer index of the control group sample of table three
| Control group sample | Risk of cancer index |
| GSM1200304 | 0.805993 |
| GSM1200305 | 5.811704 |
| GSM1200306 | 5.468377 |
| GSM1200307 | 5.348942 |
| GSM1200308 | 1.9E-05 |
| GSM1200309 | 1.017762 |
| GSM1200310 | 2.184581 |
| GSM1200311 | 1.959261 |
| GSM1200312 | 7.340933 |
| GSM1200313 | 0.413556 |
The risk of cancer index of the liver cancer sample of table four
| Liver cancer sample | Risk of cancer index |
| GSM1200294 | 19.44 |
| GSM1200295 | 14.80 |
| GSM1200296 | 11.80 |
| GSM1200297 | 14.44 |
| GSM1200298 | 16.03 |
| GSM1200299 | 16.19 |
| GSM1200300 | 4.19 |
| GSM1200301 | 22.02 |
| GSM1200302 | 7.03 |
| GSM1200303 | 13.59 |
The method of presence risk based on above-mentioned, of the invention detection cancer, it is to utilize the individual of measurement one and non-cancer
The expression quantity of 18 cancer gene marks, recycles the gene expression amount of colony as basis in the blood sample of disease control group
Value is influenceed with to reduce individual and the method that is weighted to gene calculates the dangerous index of cancer point, and the risk of cancer index is commenting
Estimate the reaction and prognosis situation of the presence risk and a patient of an individual cancer after treatment of cancer is received.Therefore, it is of the invention
Method can be applied to preventive health-care medicine to assess cancer potential risk；Treatment of cancer recruitment evaluation is treated at present with aided assessment
It is whether effective；Applied to cancer tracking prognosis to assess cancer relapse risk.
Claims (8)
1. a kind of method for the presence risk for detecting cancer, its step include：
The corpse or other object for laboratory examination and chemical testing sample of the body fluid comprising nucleic acid is obtained from subject；
Measure cancer gene mark group mrna expression amount, the cancer gene mark group be by betaglobulin, glycosylated hemoglobin,
Cytohormone message mortifier -3, adrenomedulin, secreting type Leucoprotease suppress albumen, surface antigen differentiation cluster
68th, S100 calbindins P, DNA damage induction transfer factor 3, Ctsz, Bcl-2 correlations X protein, amyloid
Forerunner's albumen, turn keto-alcohol ferment enzyme, G-protein coupling ERs, Hemopexin and Hemopexin correlation
Albumen, FKBPL 3, acid phosphatase 5, lysosome related protein cross-film 4alpha and Chemokine receptor4 institute group
Into；
The risk of cancer index of the subject is calculated, its formula is the sum [LN (underlying tables of Individual genes performance amount/Individual genes
Up to amount)], comprising：
(i) the basal expression amount of an Individual genes expression quantity divided by an Individual genes is taken to calculate the expression of each gene times
Rate；
(ii) natural logrithm is taken rising multiple or decline multiple is had identical weight multiplying power again；
(iii) gene expression amount ascensionist confirms the presence risk for having cancer, and gene expression amount descender does not consider；And
(iv) the risk of cancer index that the genes of individuals expression affiliated weight of ascensionist is subject is added up；
The basal expression amount of the Individual genes is taken from the corresponding of the corpse or other object for laboratory examination and chemical testing sample of the body fluid containing nucleic acid of non-cancer control group
The geometric mean of the expression quantity of cancer gene；And
The risk of cancer index of non-cancer control group is calculated with step (c)；
Risk of cancer index wherein based on the subject is less than the median person of the risk of cancer index of the non-cancer control group,
It is to represent the subject there is the low-risk for forming cancer；Risk of cancer index based on the subject is higher than the non-cancer control
The credibility interval person of risk of cancer index 99% of group, representing the subject has the excessive risk for forming cancer.
2. according to the method for claim 1, it is characterised in that the step (b) is via micro- array chip, real time aggregation
Enzyme chain reaction, Northern markings hybrid method or in situ hybridization measure.
3. according to the method for claim 1, it is characterised in that the cancer is for breast cancer, stomach cancer, carcinoma of urinary bladder or liver cancer.
4. according to the method for claim 1, it is characterised in that the corpse or other object for laboratory examination and chemical testing sample is for PMBC sample.
5. a kind of assess method of the patient to the prognosis recurrence risk for the treatment of of cancer, its step includes：
The corpse or other object for laboratory examination and chemical testing sample of the body fluid comprising nucleic acid is obtained from patient；
Measure cancer gene mark group mrna expression amount, the cancer gene mark group be by betaglobulin, glycosylated hemoglobin,
Cytohormone message mortifier -3, adrenomedulin, secreting type Leucoprotease suppress albumen, surface antigen differentiation cluster
68th, S100 calbindins P, DNA damage induction transfer factor 3, Ctsz, Bcl-2 correlations X protein, amyloid
Forerunner's albumen, turn keto-alcohol ferment enzyme, G-protein coupling ERs, Hemopexin and Hemopexin correlation
Albumen, FKBPL 3, acid phosphatase 5, lysosome related protein cross-film 4alpha and chemokine receptors institute group
Into；
The risk of cancer index of the patient is calculated, its formula is
Sum [LN (the basal expression amounts of Individual genes expression quantity/Individual genes)], comprising：
(i) the basal expression amount of an Individual genes expression quantity divided by an Individual genes is taken to calculate the expression of each gene times
Rate；
(ii) natural logrithm is taken rising multiple or decline multiple is had identical weight multiplying power again；
(iii) gene expression amount ascensionist confirms the presence risk for having cancer, and gene expression amount descender does not consider；And
(iv) the risk of cancer index that the genes of individuals expression affiliated weight of ascensionist is patient is added up；
The basal expression amount of the Individual genes is taken from the corresponding of the corpse or other object for laboratory examination and chemical testing sample of the body fluid containing nucleic acid of non-cancer control group
The geometric mean of the expression quantity of cancer gene；
The risk of cancer index of non-cancer control group is calculated with step (c)；
Risk of cancer index wherein based on the patient is less than the median person of the risk of cancer index of the non-cancer control group, is
Representing the patient has the low-risk of cancer return；Risk of cancer index based on the patient is higher than the cancer of the non-cancer control group
The credibility interval person of disease risk index 99%, representing the patient has the excessive risk of cancer return.
6. according to the method for claim 5, it is characterised in that the step (b) is via micro- array chip, real time aggregation
Enzyme chain reaction, Northern markings hybrid method or in situ hybridization measure.
7. according to the method for claim 5, it is characterised in that the cancer is breast cancer, stomach cancer, carcinoma of urinary bladder or liver cancer.
8. according to the method for claim 5, it is characterised in that the corpse or other object for laboratory examination and chemical testing sample is PMBC sample.
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| CN108335812A (en) * | 2018-03-13 | 2018-07-27 | 海宁市天丰磁业有限公司 | A kind of production technology of composite magnetic |
| CN108648826A (en) * | 2018-05-09 | 2018-10-12 | 中国科学院昆明动物研究所 | A kind of cancer of pancreas personalization prognostic evaluation methods based on multi-gene expression characteristic spectrum |
| CN111354421A (en) * | 2018-12-24 | 2020-06-30 | 奎克生技光电股份有限公司 | Health Risk Assessment Methods |
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| US20210027890A1 (en) * | 2019-07-24 | 2021-01-28 | ConnSante BioTech, Inc. | Detecting, evaluating and predicting system for cancer risk |
| TWI845024B (en) * | 2022-11-15 | 2024-06-11 | 長庚大學 | Methods for colorectal cancer diagnosis and prognosis |
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| CN101365802A (en) * | 2005-10-28 | 2009-02-11 | 生物梅里埃股份公司 | Method for detecting cancer |
| CN104364654A (en) * | 2012-05-11 | 2015-02-18 | 弗莱德哈钦森癌症研究中心 | Methods for predicting and detecting cancer risk |
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| CN108335812A (en) * | 2018-03-13 | 2018-07-27 | 海宁市天丰磁业有限公司 | A kind of production technology of composite magnetic |
| CN108648826A (en) * | 2018-05-09 | 2018-10-12 | 中国科学院昆明动物研究所 | A kind of cancer of pancreas personalization prognostic evaluation methods based on multi-gene expression characteristic spectrum |
| CN108648826B (en) * | 2018-05-09 | 2022-04-15 | 中国科学院昆明动物研究所 | Pancreatic cancer personalized prognosis evaluation method based on polygene expression profile |
| CN111354421A (en) * | 2018-12-24 | 2020-06-30 | 奎克生技光电股份有限公司 | Health Risk Assessment Methods |
Also Published As
| Publication number | Publication date |
|---|---|
| TWI600767B (en) | 2017-10-01 |
| TW201802247A (en) | 2018-01-16 |
| KR101914348B1 (en) | 2018-11-01 |
| KR20180007291A (en) | 2018-01-22 |
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