CN108287984A - The accurate processing method of polygene combined faeces DNA DNA methylation assay data - Google Patents
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Abstract
The present invention provides a kind of accurate processing methods of polygene combined faeces DNA DNA methylation assay data, including first obtain gene data to be detected, then cdna sample data to be detected are obtained from gene data to be detected;And a variety of multiple gene associations are carried out to cdna sample data to be detected and are detected, the positive rate of each joint-detection is obtained respectively;P values are obtained to the positive rate chi-square criterion of each joint-detection, current multiple gene associations are detected as optimal multiple gene association detection modes if P values are more than setting P value ratios;Gene data to be detected is detected finally by optimal multiple gene association detection modes and obtains current detection data.The testing result of such joint-detection mode of the present invention is more accurate, and positive rate and specificity are high and at low cost, can be used for the clinical sensibilisin and specificity of screening early stage CRC.
Description
Technical field
The present invention relates to medicine technology field more particularly to a kind of polygene combined faeces DNA DNA methylation assay data
Accurate processing method.
Background technology
Colorectal cancer (Colorectal cancer, CRC) is most commonly seen malignant tumor of digestive tract, in recent years with
The continuous improvement of living standard, the incidence of CRC rises year by year, but majority of cases is mostly just diagnosed in the middle and advanced stage stage, in advance
Bad afterwards, the death rate is high.Its early symptom is not true to type, if early detection can obviously improve prognosis, improves patient survival, reduces
The death rate.The method for clinically commonly using screening colorectal cancer at present includes mainly that electronics Colon and rectum microscopy is surveyed and fecal occult blood examination
(fecal occul tblood test, FOBT) is tested, is limited respectively because it is invasive inspection or the disadvantages such as positive rate is low
The extensive use in CRC screenings is made.
In recent years, DNA methylation be acknowledged as epigenetics cause cancer especially CRC develop it is important because
Element, multinomial guide have explicitly pointed out the method that DNA methylation assay can be used as the screening of early stage CRC.Simultaneously because it belongs to Noninvasive inspection
It looks into, patient acceptance is with compliance obviously higher than colonoscopy.Blood plasma Septin9 methylating reagent boxes, which are widely used in, to be faced
Bed, recall rate and specificity to CRC are significantly better than that FOBT is detected, but its testing cost is higher, and patient is often difficult to connect
By.
Since tumour cell can persistently fall off from intestinal mucosal surface and be excreted with excrement, fecal sample also can be used
In DNA methylation screening.Mass data shows that the positive rate of faeces DNA DNA methylation assay and specificity obviously exceed blood
Liquid sample.However, the recall rate and specificity of single-gene faeces DNA DNA methylation assay diagnosis CRC are relatively low, although polygene combined
Recall rate, but increasing with joint-detection gene number can be improved by carrying out DNA methylation assay, and cost can also increase, high-cost
Detection method is simply not proposed to a wide range of CRC early screenings work, therefore finds with high positive recall rate and specificity
Simultaneously, moreover it is possible to the most suitable assortment of genes of testing cost is reduced, it is significant for CRC screenings.
Invention content
For the drawbacks described above and problem of the prior art, the purpose of the embodiment of the present invention is to provide a kind of polygene combined
The accurate processing method of faeces DNA DNA methylation assay data, processing method of the invention are capable of providing a kind of with positive detection
The most sensitive and minimum testing cost CRC gene screenings combination of rate highest, specificity.
In order to achieve the above object, the present invention provides the following technical solutions:
The accurate processing method of polygene combined faeces DNA DNA methylation assay data, includes the following steps:
Gene data to be detected is obtained, cdna sample data to be detected are obtained from the gene data to be detected;
A variety of multiple gene association detections are carried out to the cdna sample data to be detected, obtain each joint-detection respectively
Positive rate;
P values are obtained to the positive rate chi-square criterion of each joint-detection, if the P values are more than setting P value ratios
Current multiple gene associations are detected as optimal multiple gene association detection modes;
It is current that acquisition is detected to the gene data to be detected by optimal multiple gene association detection modes
Detection data.
Further, a variety of multiple gene association detection projects are:CNRIP1/SNCA、CNRIP1/SFRP2、
CNRIP1/Vimentin、SNCA/SFRP2、SNCA/Vimentin、SFRP2/Vimentin、CNRIP1/SNCA/SFRP2、
CNRIP1/SNCA/Vimentin、CNRIP1/SFRP2/Vimentin、SNCA/SFRP2/Vimentin、CNRIP1/SNCA/
SFRP2/Vimentin。
Further, the P values ratio that sets is 0.05.
Further, the accurate processing method of polygene combined faeces DNA DNA methylation assay data of the invention is also wrapped
It includes:
Receive cdna sample data to be detected.
Further, the accurate processing method of polygene combined faeces DNA DNA methylation assay data of the invention is also wrapped
It includes:
Current detection data are shown.
A kind of accurate processing method of polygene combined faeces DNA DNA methylation assay data provided by the invention, has
Beneficial effect is:The accurate processing method of polygene combined faeces DNA DNA methylation assay data through the invention, will be classical
Vimentin and SFRP2 genes and newly discovered CNRIP1 and SNCA gene associations carry out DNA methylation assay, with find most
Good combination screening CRC.In a variety of multiple gene association detections, optimal multiple gene association detection modes are preferentially obtained, and
Current detection data is obtained by this optimal multiple gene association detection mode.The testing result of such joint-detection mode
More accurate, positive rate and specificity are high, can be used for the clinical sensibilisin and specificity of screening early stage CRC.
In addition, by being screened to a variety of multiple gene association detection modes, clinical samples verification tip is therein
The clinical sensibilisin and specificity of SNCA/SFRP2/Vimentin genes are 88.2%, 84.1%;With CRC commercial kits
Testing result compare no significant difference, and expense, compared with CRC commercial kit relative moderates, operating process is also relatively easy.
The polygenes faeces DNA joint-detection that methylates can significantly improve the clinical sensibilisin and specificity of screening early stage CRC,
Compared with detection methods such as FOBT, electronics Colon and rectum mirror, blood methylation detection kits, there is Noninvasive, hurtless measure, operation letter
Just the advantages that, cost is relatively low, positive rate and specificity are higher, is expected to be used for the screening of clinical extensive CRC.
Description of the drawings
In order to more clearly explain the embodiment of the invention or the technical proposal in the existing technology, to embodiment or will show below
There is attached drawing needed in technology description to be briefly described, it should be apparent that, the accompanying drawings in the following description is only this
Some embodiments of invention without having to pay creative labor, may be used also for those of ordinary skill in the art
With obtain other attached drawings according to these attached drawings.
Fig. 1 is the accurate processing method connection signal of the polygene combined faeces DNA DNA methylation assay data of the present invention
Figure.
Specific implementation mode
Below in conjunction with the embodiment of the present invention, technical scheme of the present invention is clearly and completely described, it is clear that
Described embodiments are only a part of the embodiments of the present invention, instead of all the embodiments.Based on the implementation in the present invention
Example, the every other embodiment that those of ordinary skill in the art are obtained without creative efforts belong to
The scope of protection of the invention.
According to Fig. 1.The accurate processing method of the polygene combined faeces DNA DNA methylation assay data of the present invention,
Include the following steps:
Gene data S100 to be detected is obtained first, is received from above-mentioned gene data to be detected and shows cls gene to be checked
Sample data carries out a variety of multiple genes after obtaining cdna sample data S101 to be detected to above-mentioned cdna sample data to be detected
Joint-detection S102 obtains the positive rate χ 2S103 of each joint-detection respectively;
Currently preferred above-mentioned a variety of multiple gene association detection projects are:CNRIP1/SNCA、CNRIP1/SFRP2、
CNRIP1/Vimentin、SNCA/SFRP2、SNCA/Vimentin、SFRP2/Vimentin、CNRIP1/SNCA/SFRP2、
CNRIP1/SNCA/Vimentin、CNRIP1/SFRP2/Vimentin、SNCA/SFRP2/Vimentin、CNRIP1/SNCA/
SFRP2/Vimentin。
Wherein, when two gene association detections, the positive rate of CNRIP1/SNCA joint-detections CRC is 85.0%,
The positive rate of CNRIP1/SFRP2 joint-detections CRC is the positive of 91.7%, CNRIP1/Vimentin joint-detections CRC
The positive rate that recall rate is 93.3%, SNCA/SFRP2 joint-detections CRC is 83.3%, SNCA/Vimentin joint inspections
The positive rate that the positive rate for surveying CRC is 91.7%, SFRP2/Vimentin joint-detections CRC is 91.7%, specifically
Property is respectively 88.0%, 84.0%, 92.0%, 84.0%, 92.0%, 88.0%.
When three gene association detections, the positive rate of CNRIP1/SNCA/SFRP2 joint-detections CRC is 93.3%,
The positive rate of CNRIP1/SNCA/Vimentin joint-detections CRC is 96.7%, SNCA/SFRP2/Vimentin joint inspections
Survey the positive rate of CRC is for the positive rate of 96.7%, CNRIP1/SFRP2/Vimentin joint-detections CRC
98.3%, specificity is respectively 88.0%, 80.0%, 84.0%, 80.0%.
When four gene association detections, the positive rate of CNRIP1/SNCA/SFRP2/Vimentin joint-detections CRC
It is 100.0%, specificity is 80.0%.
P values are obtained to the positive rate chi-square criterion of above-mentioned each joint-detection, if above-mentioned P values are more than setting P value ratios
S104, then currently multiple gene associations are detected as optimal multiple gene association detection mode S105;Wherein, setting P of the invention
Value ratio is 0.05.P values, wherein SNCA/SFRP2/ are obtained by the positive rate chi-square criterion to above-mentioned each joint-detection
The positive rate of Vimentin is 96.7%, specificity 84.0%, the positive of CNRIP1/SNCA/SFRP2/Vimentin
Recall rate is 100.0%, and specificity is 80.0%, is two groups of optimal multiple gene association detection modes, and therebetween without bright
Aobvious significant difference, but in order to effectively control testing cost, then can determine that SNCA/SFRP2/Vimentin is optimal multiple
Gene association detection mode.
By above-mentioned optimal multiple gene association detection mode SNCA/SFRP2/Vimentin, to above-mentioned cls gene to be checked
Data, which are detected, obtains current detection data S106, and is shown to current detection data.This detection mode is not only positive
Property recall rate and specificity are excellent, and are effectively controlled testing cost.
Clinical verification:
Choose in December, 2014 to moved in during in November, 2015 Tang Dou hospitals of The Fourth Military Medical University GI Medicine be hospitalized
Patient, the research object as this experiment.Research object is screened, CRC high risk factors include:(1) it has blood in stool, mucus
Just, the symptoms of digestive tract such as abdominal pain;(2) once there is colorectal cancer medical history person;(3) age is at 50-74 Sui;(4) it once suffered from Colorectal Adenomas, burst
Disease before the correlation Colonic Carcinoma such as ulcer colitis, Crohn disease, snail fever;(5) lineal relative of large intestine family breast cancer;
(6) there is the lineal relative of colorectal polyp family history;(7) there is pelvic irradiation history;(8) life styles such as smoking, diet, obesity because
Element;(9) diabetes B.The excrement of 200 patients is collected altogether as detection sample, and all excrement marks are patient's early morning nature
The excrement of discharge.
1, colorectal cancer commercial kit detects
The stool sample of 200 patients collected is detected with colorectal cancer commercial kit.Detection content includes
Three aspects are that Kras gene magnifications, methylated genes detect in hemoglobin detection, excrement in excrement respectively, this kit
The stool sample of collection is detected by these three methods, finally carries out comprehensive score, to which whether diagnosis suffers from CRC.
Wherein, there are 34 with kit tests positive, wherein in 17 patients for being diagnosed as CRC through enteroscopy, use reagent
Box tests positive has 16.In 200 patients, the patient for showing false positive has 18.Statistical analysis, colorectal cancer
The clinical sensibilisin of commercial kit screening CRC is 94.1% (16/17), and specificity is 90.2% (165/183).
2, the result of tri- gene association screening CRC of SNCA/SFRP2/Vimentin
The goldstandard that reference is diagnosed using enteroscopy result and pathological examination as CRC is being included in 200 of screening object
In patient, there are 17 people to be diagnosed as CRC through enteroscopy.Tri- gene associations of statistical analysis SNCA/SFRP2/Vimentin are examined
The clinical sensibilisin of disconnected CRC is 88.2% (15/17), and specificity is 84.1% (154/183).
3, excrement DNA methylation assay and colorectal cancer the commercial kit detection of the SNCA/SFRP2/Vimentin assortments of genes
Results contrast.
By the clinical sensibilisin and specificity of tri- gene methylation joint-detection CRC of SNCA/SFRP2/Vimentin
The clinical sensibilisin and specificity (94.1%, 90.2%) of (88.2%, 84.1%) and colorectal cancer commercial kit carry out group
Between rate comparison, have no statistically significant difference.
It is above-mentioned the experimental results showed that, it is quick that screening its clinic is carried out to CRC patient by the method for faeces DNA DNA methylation assay
The testing result no significant difference of perception and specificity and colorectal cancer commercial kit, and excrement DNA methylation assay is relatively commercialized
Kit operating process is more easy, and testing cost is relatively low.
Therefore, the accurate processing method of polygene combined faeces DNA DNA methylation assay data of the invention obtains most
Excellent multiple gene association detection modes have higher clinical sensibilisin and specificity, the current clinically common detection side of comparison
Method shows clear superiority, and not only operating procedure is simple, and inspection cost is relatively low.
The above description is merely a specific embodiment, but scope of protection of the present invention is not limited thereto, any
Those familiar with the art in the technical scope disclosed by the present invention, can easily think of the change or the replacement, and should all contain
Lid is within protection scope of the present invention.Therefore, the protection scope of the present invention shall be subject to the protection scope of the claims.
Claims (5)
1. the accurate processing method of polygene combined faeces DNA DNA methylation assay data, includes the following steps:
Gene data to be detected is obtained, cdna sample data to be detected are obtained from the gene data to be detected;
A variety of multiple gene association detections are carried out to the cdna sample data to be detected, obtain the positive of each joint-detection respectively
Recall rate;
P values are obtained to the positive rate chi-square criterion of each joint-detection, it is current if the P values are more than setting P value ratios
Multiple gene associations are detected as optimal multiple gene association detection modes;
Acquisition current detection is detected to the gene data to be detected by optimal multiple gene association detection modes
Data.
2. the accurate processing method of polygene combined faeces DNA DNA methylation assay data according to claim 1, special
Sign is that a variety of multiple gene association detection projects are:CNRIP1/SNCA、CNRIP1/SFRP2、CNRIP1/
Vimentin、SNCA/SFRP2、SNCA/Vimentin、SFRP2/Vimentin、CNRIP1/SNCA/SFRP2、CNRIP1/
SNCA/Vimentin、CNRIP1/SFRP2/Vimentin、SNCA/SFRP2/Vimentin、CNRIP1/SNCA/SFRP2/
Vimentin。
3. the accurate processing method of polygene combined faeces DNA DNA methylation assay data according to claim 1 or 2,
It is characterized in that, the P values ratio that sets is 0.05.
4. the accurate processing method of polygene combined faeces DNA DNA methylation assay data according to claim 1 or 2,
It is characterised in that it includes:
Receive cdna sample data to be detected.
5. the accurate processing method of polygene combined faeces DNA DNA methylation assay data according to claim 1 or 2,
It is characterised in that it includes:
Current detection data are shown.
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CN104480215A (en) * | 2014-12-30 | 2015-04-01 | 宁波有成生物医药科技有限公司 | Gene joint detection method and kit |
CN106755466A (en) * | 2017-01-12 | 2017-05-31 | 宁夏医科大学 | A kind of its method for building up of specific DNA methylome and application |
Non-Patent Citations (1)
Title |
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