CN109811057A - Application of hypoxia-related genes in colorectal cancer prediction system - Google Patents
Application of hypoxia-related genes in colorectal cancer prediction system Download PDFInfo
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- CN109811057A CN109811057A CN201910242114.XA CN201910242114A CN109811057A CN 109811057 A CN109811057 A CN 109811057A CN 201910242114 A CN201910242114 A CN 201910242114A CN 109811057 A CN109811057 A CN 109811057A
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- 206010009944 Colon cancer Diseases 0.000 title claims abstract description 53
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- 238000004393 prognosis Methods 0.000 claims abstract description 23
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Abstract
本发明提供了缺氧相关基因在结直肠癌预测系统中的应用，本发明结合缺氧相关基因，找到一组可以稳定预测II/III期结直肠癌预后的12个缺氧相关基因；在不需要使用标准化技术平台统一测量前提下，可以兼容任何类型的测量平台来预测II/III期结直肠癌的预后。
The invention provides the application of hypoxia-related genes in a colorectal cancer prediction system. The invention combines hypoxia-related genes to find a group of 12 hypoxia-related genes that can stably predict the prognosis of stage II/III colorectal cancer; Under the premise of unified measurement using a standardized technology platform, it can be compatible with any type of measurement platform to predict the prognosis of stage II/III colorectal cancer.
Description
Technical field
The present invention relates to application of the anoxic related gene in colorectal cancer forecasting system.
Background technique
Colorectal cancer (CRC) is one of world's common cancer, is had every year close to 1,400,000 new cases.Although new treatment side
Case emerges one after another, but 5 annual survival rates only have 55%.Operative treatment is determined as a line scheme according to traditional clinical feature
Justice is same type of patient, and the outcome after treatment also has very big difference.Recent study thinks that this mainly has cancer
The molecular heterogeneity of patient causes.
Gene molecule marker refers to the expression based on one group of gene, by machine learning founding mathematical models, for pre-
Survey objectives clinically.Gene expression detection means are quite mature in recent years, and skill is sequenced including high-throughput RNA
Art, microarray technology (Microarray), and opposite small throughput real-time quantitative polymerase chain reaction (RT-qPCR) and
NanoString technology etc..But one group of assortment of genes for colorectal cancer prognosis prediction how is found, and the number of optimization
Model is learned for predicting, and good result can be reached, it is known that research it is less.
Anoxic related gene is pointed out that the generation and development of cancer have risen most important by numerous studies in recent years
Effect.In particular, the development of immune microenvironment and colorectal cancer is closely connected, it is related to anoxic.But it is rare at present
Colorectal cancer prognosis is predicted with anoxic related gene and does not have broad scale research.
The major defect of the prior art: effect of the anoxic related gene in colorectal cancer is not organically combined, and is not had
It is verified on a large scale.Importantly, the existing assortment of genes has problems when in use, for example, many product requirements
A whole set of kit must be used, needs to re-measure patient just under the premise of complete standard and can be carried out prediction, other are surveyed
Amount means are without compatibility.
Summary of the invention
It provides anoxic related gene it is an object of the invention to overcome the shortcomings of the prior art place and is tying directly
In the expression of the 12 anoxic related genes filtered out, and generation, are sent out in application in intestinal cancer forecasting system by the detection present invention
Entering in risk model can prognostic risk after the treatment of accurate judgement II/III phase Patients with Colorectal Cancer.
To achieve the above object, the technical solution taken: gene TNFAIP8, ORAI3, MINPP1, MBTD1, TRAF3,
CYB5R3, ZBTB44, CASP6, DTX3L, FAM117B, PRELID2 and IRF1's is used in combination in preparation for predicting II/III
Application in the kit of phase Patients with Colorectal Cancer prognosis.
In addition, the present invention also provides the reagent of the expression of detection anoxic related gene in preparation for predicting II/III
Application in the kit of phase Patients with Colorectal Cancer prognosis, the reagent for detect gene TNFAIP8, ORAI3, MINPP1,
The mRNA expression of MBTD1, TRAF3, CYB5R3, ZBTB44, CASP6, DTX3L, FAM117B, PRELID2 and IRF1.
In addition, the present invention also provides a kind of for predicting the kit of II/III phase Patients with Colorectal Cancer prognosis comprising
For detect detection gene TNFAIP8, ORAI3, MINPP1, MBTD1, TRAF3, CYB5R3, ZBTB44, CASP6, DTX3L,
The reagent of the mRNA expression of FAM117B, PRELID2 and IRF1.
In addition, the present invention also provides a kind of systems for predicting II/III phase Patients with Colorectal Cancer prognosis comprising:
Data input module, for the result of the mRNA expression value of the anoxic related gene of Patients with Colorectal Cancer to be inputted mould
Type computing module, the anoxic related gene include gene TNFAIP8, ORAI3, MINPP1, MBTD1, TRAF3, CYB5R3,
ZBTB44, CASP6, DTX3L, FAM117B, PRELID2 and IRF1；The mRNA expression value is to pass through Bioconductor's
GEOquery package standardization treated mRNA expression data；
Model computation module, including LASSO Cox risk model, for according to Patients with Colorectal Cancer anoxic related gene
MRNA expression value and LASSO Cox risk model calculate patient's risk score；The calculation formula of the risk score are as follows: Risk
Score=-0.006 × exp (the mRNA expression value of TNFAIP8)+0.052 × exp (the mRNA expression value of ORAI3) -0.079 ×
Exp (the mRNA expression value of MINPP1) -0.023 × exp (the mRNA expression value of MBTD1) -0.087 × exp (mRNA of TRAF3
Expression value)+0.005 × exp (the mRNA expression value of CYB5R3) -0.050 × exp (the mRNA expression value of ZBTB44) -0.019 ×
Exp (the mRNA expression value of CASP6) -0.003 × exp (the mRNA expression value of DTX3L) -0.059 × exp (mRNA of FAM117B
Expression value) -0.023 × exp (the mRNA expression value of PRELID2) -0.070 × exp (the mRNA expression value of IRF1), high risk group
With the cutoff value -0.083 of low-risk group；
As a result output module, it is pre- after Patients with Colorectal Cancer is treated for being predicted according to Patients with Colorectal Cancer risk score
Risk afterwards；When Patients with Colorectal Cancer risk score >=-0.083, Patients with Colorectal Cancer is high risk, existence can significance difference, need
It will more clinical concerns and better clinical management；As Patients with Colorectal Cancer risk score < -0.083, Colon and rectum carninomatosis
Artificial low-risk, existence preferably, can use the therapeutic scheme of milder, avoid over-treatment.
The beneficial effects of the present invention are: the present invention provides anoxic related gene answering in colorectal cancer forecasting system
With present invention combination anoxic related gene, finding one group can be with 12 anoxic of stability forecast II/III phase colorectal cancer prognosis
Related gene；Under the premise of not needing using standardized technique platform unified measurement, any kind of measuring table can be compatible with
To predict the prognosis of II/III phase colorectal cancer；In addition, the present invention has also carried out single argument and multi-variables analysis, it was demonstrated that use this
The anoxic risk score (Hypoxia risk) that risk model calculates really can be with independent prediction Patients with Colorectal Cancer prognostic risk.
Detailed description of the invention
Figure 1A shows the calculation formula of anoxic related gene prediction model, and Figure 1B shows the best cutoff of high-risk patient
Value；
Fig. 2 is to carry out Patients with Colorectal Cancer prognostic analysis using the anoxic related gene model built；Wherein, scheme a, d,
G shows that anoxic correlation levies gene constructed colorectal cancer prognostic model to training, validation-1 and validation-
2 three queue patients carry out distribution (abscissa) overview whether risk score (ordinate) and the recurrence of II/III phase colorectal cancer
Figure；Scheme b, e, h show anoxic related gene building colorectal cancer prognostic model combination training, validation-1 and
The ROC curve figure of the queue Patients with Colorectal Cancer 2 years of validation-2 tri-, 3 years and 5 years follow-up information, AUC is (under curve
Area) embody anoxic related gene have good Patients with Colorectal Cancer prognosis prediction effect；Scheme c, f, i and shows anoxic dependency basis
Because the anoxic high risk group and low-risk group of model partition are in tri- teams of training, validation-1 and validation-2
Survivorship curve figure in column, HR (Hazard ratio) embodies the high risk group that anoxic related gene divides can effectively draw with low-risk group
Divide the DFS (no tumor life span), P < 0.05 of Patients with Colorectal Cancer.
Specific embodiment
To better illustrate the object, technical solutions and advantages of the present invention, below in conjunction with specific embodiments and the drawings pair
The present invention is described further.
Embodiment 1
The excavation of colorectal cancer prognosis anoxic related gene
Use the data set that the number in open high throughput GEO database is GSE39582 as exploitation data set, measures
Platform is the microarray platform of Affymetrix company, includes 566 Patients with Colorectal Cancer samples, calls CIT microarray data in the following text
Collection.Wherein, 520 patients have complete clinical prognosis information, and 300 were not done chemotherapy.Anoxic related gene is from ImmPort number
It is obtained according to library, adds up to 3444 genes, 49 classification.Wherein 1636 anoxic related genes are surveyed on CIT microarray dataset
It has measured and there were significant differences (Median Absolute Deviation is greater than 0.5) for expression between different patients.Into one
Step carries out 1000 sampling analyses using resampling technique, finds and stablizes relevant 40 anoxic related genes to prognosis.
Building is used for the anoxic related gene of colorectal cancer prognosis prediction
According to the prognosis information of patient, using LASSO Cox model, 40 anoxic related genes are reduced to 12 bases
Cause: gene TNFAIP8, ORAI3, MINPP1, MBTD1, TRAF3, CYB5R3, ZBTB44, CASP6, DTX3L, FAM117B,
PRELID2 and IRF1.
The foundation of prognostic model
Using 12 anoxic related genes, establish prediction model, and by the verifying of extensive sample (6 independent data sets,
1877 patients) it proves significantly predict patient's prognosis really；The calculation formula of risk score are as follows: Risk score=-
0.006 × exp (the mRNA expression value of TNFAIP8)+0.052 × exp (the mRNA expression value of ORAI3) -0.079 × exp
(mRNA of TRAF3 is expressed (the mRNA expression value of MINPP1) -0.023 × exp (the mRNA expression value of MBTD1) -0.087 × exp
Value)+0.005 × exp (the mRNA expression value of CYB5R3) -0.050 × exp (the mRNA expression value of ZBTB44) -0.019 × exp
(the mRNA expression value of CASP6) -0.003 × exp (the mRNA expression value of DTX3L) -0.059 × exp (mRNA table of FAM117B
Up to value) -0.023 × exp (the mRNA expression value of PRELID2) -0.070 × exp (the mRNA expression value of IRF1), ROC curve stroke
Divide the cutoff value -0.083 of anoxic high risk group and low-risk group；See Fig. 1 and table 1.
Each gene function of table 1 and its specific gravity β in a model
Embodiment 2Colorectal cancer prognosis is predicted using this model
As shown in Fig. 2, carrying out Patients with Colorectal Cancer prognostic analysis using the anoxic related gene model built, as a result show
Show that anoxic related gene has good Patients with Colorectal Cancer prognosis prediction effect.
In addition, as shown in table 2, the present invention has also carried out single argument and multi-variables analysis, it was demonstrated that use model meter of the present invention
The anoxic risk score (Hypoxia risk) of calculation really can be with independent prediction Patients with Colorectal Cancer prognostic risk.
Table 2
Finally, it should be noted that the above embodiments are merely illustrative of the technical solutions of the present invention rather than protects to the present invention
The limitation of range is protected, although the invention is described in detail with reference to the preferred embodiments, those skilled in the art should
Understand, it can be with modification or equivalent replacement of the technical solution of the present invention are made, without departing from the essence of technical solution of the present invention
And range.
Claims (4)
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110317879A (en) * | 2019-08-19 | 2019-10-11 | 中山大学附属第六医院 | Application, colorectal cancer prognosis prediction kit and the forecasting system of gene detection reagent |
| CN112245584A (en) * | 2020-10-20 | 2021-01-22 | 浙江大学 | Use of polyphosphoinositide phosphatase 1 as a target molecule |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101389957A (en) * | 2005-12-23 | 2009-03-18 | 环太平洋生物技术有限公司 | Prognosis prediction for colorectal cancer |
| US20140212415A1 (en) * | 2011-08-04 | 2014-07-31 | Myriad Genetics, Inc. | Hypoxia-related gene signatures for cancer classification |
| US20170298443A1 (en) * | 2014-09-25 | 2017-10-19 | Moffitt Genetics Corporation | Prognostic tumor biomarkers |
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2019
- 2019-03-27 CN CN201910242114.XA patent/CN109811057B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101389957A (en) * | 2005-12-23 | 2009-03-18 | 环太平洋生物技术有限公司 | Prognosis prediction for colorectal cancer |
| US20140212415A1 (en) * | 2011-08-04 | 2014-07-31 | Myriad Genetics, Inc. | Hypoxia-related gene signatures for cancer classification |
| US20170298443A1 (en) * | 2014-09-25 | 2017-10-19 | Moffitt Genetics Corporation | Prognostic tumor biomarkers |
Non-Patent Citations (1)
| Title |
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| MARISA L等: "Series GSE39582", 《GEO》 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110317879A (en) * | 2019-08-19 | 2019-10-11 | 中山大学附属第六医院 | Application, colorectal cancer prognosis prediction kit and the forecasting system of gene detection reagent |
| CN112245584A (en) * | 2020-10-20 | 2021-01-22 | 浙江大学 | Use of polyphosphoinositide phosphatase 1 as a target molecule |
| CN112245584B (en) * | 2020-10-20 | 2022-02-11 | 浙江大学 | Use of polyphosphate inositol phosphatase 1 as target molecule |
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