CN110229909A - Detect application, kit and the head and neck cancer prognostic risk prediction meanss of the reagent of gene involved in immunity expression quantity - Google Patents
Detect application, kit and the head and neck cancer prognostic risk prediction meanss of the reagent of gene involved in immunity expression quantity Download PDFInfo
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Abstract
The invention discloses application, kit and the head and neck cancer prognostic risk prediction meanss of the reagent of detection gene involved in immunity expression quantity, are related to field of biomedicine.The invention discloses the reagents of detection gene involved in immunity expression quantity in the application of head and neck cancer prognostic risk, and gene involved in immunity is selected from following gene: RFXAP, ULBP1, TMSB4Y, RBP4, LCNL1, CCR6, KLRK1, PTX3, MASP1, HRG, CCL22, OLR1, ROBO1, BTC, CHGB, DKK1, HBEGF, INHBB, PDGFA, AVPR2, IL20RA, RORB, TNFRSF18, TNFRSF25, TNFRSF4, SH3BP2 and ICOS.According to the expression quantity data of these gene involved in immunity, head and neck cancer prognostic risk is predicted, there is good specificity and sensitivity.
Description
Technical field
The present invention relates to fields of biomedicine, in particular to answering for the reagent for detecting gene involved in immunity expression quantity
With, kit and head and neck cancer prognostic risk prediction meanss.
Background technique
Head and neck cancer (head and neck cancer, HNC) is one of global common cancer, and the most common histological type is
Head and neck squamous cell carcinoma (head and neck squamous cell carcinoma, HNSCC), the annual whole world has more than
600000 new cases.Although new therapeutic scheme emerges one after another, its 5 years survival rates only about 60%, the annual whole world is about
There are 380,000 people therefore to die of illness to die.Dead major reason is the recurrence of local tumor, for there is the patient of tumor recurrence and transfer,
Position Overall survival (overall survival, OS) is only 10 to 13 months in First-line chemotherapy, and position OS is 6 in second-line chemotherapy
Month.Operative treatment is same type of patient as a line scheme, but according to traditional clinical characterizing definition, the prognosis after treatment
Effect also has very big difference.Recent study thinks that this mainly has the molecular heterogeneity of cancer patient to cause.
Gene molecule marker refers to the expression based on one group of gene, by machine learning founding mathematical models, for pre-
Survey particular problem 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 the research currently used for head and neck cancer prognosis prediction is less, shortage can preferably predict head and neck cancer
The products such as gene, reagent, the kit of prognostic risk and method.
In consideration of it, the present invention is specifically proposed.
Summary of the invention
The purpose of the present invention is to provide application, kit and the head and neck cancers of the reagent of detection gene involved in immunity expression quantity
Prognostic risk prediction meanss, to realize the prediction to head and neck cancer prognostic risk.
The present invention is implemented as follows:
Head and neck cancer prognosis is predicted in preparation in a first aspect, the present invention provides the reagents of detection gene involved in immunity expression quantity
Application in the kit of risk, above-mentioned gene involved in immunity is selected from one of following gene or a variety of combinations: RFXAP,
ULBP1、TMSB4Y、RBP4、LCNL1、CCR6、KLRK1、PTX3、MASP1、HRG、CCL22、OLR1、ROBO1、BTC、CHGB、
DKK1, HBEGF, INHBB, PDGFA, AVPR2, IL20RA, RORB, TNFRSF18, TNFRSF25, TNFRSF4, SH3BP2 and
ICOS。
Further, in some embodiments of the present invention, the gene involved in immunity in following gene one
Kind or a variety of combinations: BTC, CHGB, HBEGF, DKK1, RFXAP, RBP4, TNFRSF25, TNFRSF4, LCNL1, CCL22,
IL20RA, TNFRSF18, KLRK1, TMSB4Y and MASP1.
It is of the invention the study found that gene involved in immunity such as RFXAP, ULBP1, TMSB4Y, RBP4, LCNL1, CCR6,
KLRK1、PTX3、MASP1、HRG、CCL22、OLR1、ROBO1、BTC、CHGB、DKK1、HBEGF、INHBB、PDGFA、AVPR2、
The table of IL20RA, RORB, TNFRSF18, TNFRSF25, TNFRSF4, SH3BP2 and ICOS between different head and neck cancer patients
Up to there were significant differences, these gene involved in immunity can be used as the characterizing gene of stability forecast head and neck cancer prognosis, be exempted from according to these
The expression quantity data of epidemic disease related gene, predict head and neck cancer prognostic risk, have good specificity and sensitivity, prediction effect compared with
Good, such as 3 years AUC are up to 0.782.Therefore, the reagent for detecting the expression quantity of these gene involved in immunity can be used for preparing prediction
The kit of head and neck cancer prognostic risk.
Further, in some embodiments of the present invention, mentioned reagent is primer, and above-mentioned primer is selected from 2-28 and draws
Object centering it is one or more；
The base sequence of 2-28 primer pair is successively as follows: SEQ ID NO.3-4, SEQ ID NO.5-6, SEQ ID
NO.7-8、SEQ ID NO.9-10、SEQ ID NO.11-12、SEQ ID NO.13-14、SEQ ID NO.15-16、SEQ ID
NO.17-18、SEQ ID NO.19-20、SEQ ID NO.21-22、SEQ ID NO.23-24、SEQ ID NO.25-26、SEQ
ID NO.27-28、SEQ ID NO.29-30、SEQ ID NO.31-32、SEQ ID NO.33-34、SEQ ID NO.35-36、
SEQ ID NO.37-38、SEQ ID NO.39-40、SEQ ID NO.41-42、SEQ ID NO.43-44、SEQ ID NO.45-
46、SEQ ID NO.47-48、SEQ ID NO.49-50、SEQ ID NO.51-52、SEQ ID NO.53-54、SEQ ID
NO.55-56。
It should be noted that reagent of the present invention is not limited to primer, it is also possible to other substances, as long as energy
The component for enough detecting the expression quantity of above-mentioned gene involved in immunity is used for being prepared into the kit of prediction head and neck cancer prognostic risk
It all belongs to the scope of protection of the present invention.
Second aspect, the present invention provides a kind of kits for predicting head and neck cancer prognostic risk comprising detects immune phase
The reagent of correlation gene expression quantity, above-mentioned gene involved in immunity is selected from one of following gene or a variety of combinations: RFXAP,
ULBP1、TMSB4Y、RBP4、LCNL1、CCR6、KLRK1、PTX3、MASP1、HRG、CCL22、OLR1、ROBO1、BTC、CHGB、
DKK1, HBEGF, INHBB, PDGFA, AVPR2, IL20RA, RORB, TNFRSF18, TNFRSF25, TNFRSF4, SH3BP2 and
ICOS。
Kit provided by the invention can detecte gene involved in immunity such as RFXAP, ULBP1, TMSB4Y, RBP4,
LCNL1、CCR6、KLRK1、PTX3、MASP1、HRG、CCL22、OLR1、ROBO1、BTC、CHGB、DKK1、HBEGF、INHBB、
The expression quantity of PDGFA, AVPR2, IL20RA, RORB, TNFRSF18, TNFRSF25, TNFRSF4, SH3BP2 and ICOS, according to
Head and neck cancer prognostic risk can be predicted in these gene involved in immunity expression quantity data, has good specificity and sensitivity, prediction effect
Fruit is preferable.
Further, in some embodiments of the present invention, mentioned reagent is primer, and above-mentioned primer is selected from 2-28 and draws
Object centering it is one or more；
The base sequence of 2-28 primer pair is successively as follows: SEQ ID NO.3-4, SEQ ID NO.5-6, SEQ ID
NO.7-8、SEQ ID NO.9-10、SEQ ID NO.11-12、SEQ ID NO.13-14、SEQ ID NO.15-16、SEQ ID
NO.17-18、SEQ ID NO.19-20、SEQ ID NO.21-22、SEQ ID NO.23-24、SEQ ID NO.25-26、SEQ
ID NO.27-28、SEQ ID NO.29-30、SEQ ID NO.31-32、SEQ ID NO.33-34、SEQ ID NO.35-36、
SEQ ID NO.37-38、SEQ ID NO.39-40、SEQ ID NO.41-42、SEQ ID NO.43-44、SEQ ID NO.45-
46、SEQ ID NO.47-48、SEQ ID NO.49-50、SEQ ID NO.51-52、SEQ ID NO.53-54、SEQ ID
NO.55-56。
The third aspect, the present invention provides the methods of prediction head and neck cancer prognostic risk comprising: detect the immune of subject
The expression quantity of related gene；
Gene involved in immunity include: RFXAP, ULBP1, TMSB4Y, RBP4, LCNL1, CCR6, KLRK1, PTX3, MASP1,
HRG、CCL22、OLR1、ROBO1、BTC、CHGB、DKK1、HBEGF、INHBB、PDGFA、AVPR2、IL20RA、RORB、
TNFRSF18, TNFRSF25, TNFRSF4, SH3BP2 and ICOS.
Further, in some embodiments of the present invention, this method further include: according to the expression of gene involved in immunity
Amount calculates Risk Score value；Calculation formula is as follows:
Risk Score=0.073 × RFXAPexp+0.007 × ULBP1exp-0.117 × TMSB4Yexp+0.067 ×
RBP4exp-0.056×LCNL1exp-0.009×CCR6exp-0.093×KLRK1exp+0.037×PTX3exp-0.203×
MASP1exp+0.043×HRGexp-0.061×CCL22exp+0.04×OLR1exp-0.026×ROBO1exp+0.146×
BTCexp+0.113×CHGBexp+0.088×DKK1exp+0.109×HBEGFexp+0.009×INHBBexp+0.037×
PDGFAexp-0.043×AVPR2exp-0.067×IL20RAexp-0.01×RORBexp-0.071×TNFRSF18exp-
0.051×TNFRSF25exp-0.054×TNFRSF4exp-0.004×SH3BP2exp-0.017×ICOSexp；
Wherein, RFXAPexp, RBP4exp, ULBP1exp, TMSB4Yexp, RBP4exp, LCNL1exp, CCR6exp,
KLRK1exp、PTX3exp、MASP1exp、HRGexp、CCL22exp、OLR1exp、ROBO1exp、BTCexp、CHGBexp、
DKK1exp、HBEGFexp、INHBBexp、PDGFAexp、AVPR2exp、IL20RAexp、RORBexp、TNFRSF18exp、
TNFRSF25exp, TNFRSF4exp, SH3BP2exp, ICOSexp respectively represent RFXAP, RBP4, ULBP1, TMSB4Y, RBP4,
LCNL1、CCR6、KLRK1、PTX3、MASP1、HRG、CCL22、OLR1、ROBO1、BTC、CHGB、DKK1、HBEGF、INHBB、
The mRNA's of PDGFA, AVPR2, IL20RA, RORB, TNFRSF18, TNFRSF25, TNFRSF4, SH3BP2, ICOSexp gene
High-throughput expression value or small throughput expression value.
Further, in some embodiments of the present invention, this method further include: sentenced according to above-mentioned Risk Score value
Break the head and neck cancer prognostic risk of above-mentioned subject, if above-mentioned Risk Score value is less than or equal to predetermined value, judges above-mentioned
Subject is head and neck cancer prognosis low-risk person, if Risk Score value judges that above-mentioned subject is higher than above-mentioned predetermined value
Head and neck cancer prognosis high risk person.
Head and neck cancer prognosis low-risk person indication: head and neck cancer patient 2 years, 3 years, 5 years overall survival height, good prognosis.
Head and neck cancer prognosis high risk person indication: head and neck cancer patient 2 years, 3 years, 5 years overall survivals it is low, poor prognosis.
Further, in some embodiments of the present invention, above-mentioned predetermined value is 0.106.
Further, in some embodiments of the present invention, it is detected using 2-28 primer pair above-mentioned immunity-related
The expression quantity of cause；
The base sequence of 2-28 primer pair is successively as follows: SEQ ID NO.3-4, SEQ ID NO.5-6, SEQ ID
NO.7-8、SEQ ID NO.9-10、SEQ ID NO.11-12、SEQ ID NO.13-14、SEQ ID NO.15-16、SEQ ID
NO.17-18、SEQ ID NO.19-20、SEQ ID NO.21-22、SEQ ID NO.23-24、SEQ ID NO.25-26、SEQ
ID NO.27-28、SEQ ID NO.29-30、SEQ ID NO.31-32、SEQ ID NO.33-34、SEQ ID NO.35-36、
SEQ ID NO.37-38、SEQ ID NO.39-40、SEQ ID NO.41-42、SEQ ID NO.43-44、SEQ ID NO.45-
46、SEQ ID NO.47-48、SEQ ID NO.49-50、SEQ ID NO.51-52、SEQ ID NO.53-54、SEQ ID
NO.55-56。
Fourth aspect, the present invention provides a kind of head and neck cancer prognostic risk prediction meanss, it is pre- which is applied to head and neck cancer
Risk Forecast System afterwards, described device include data obtaining module, computing module and prediction module；
Wherein, it includes immune correlation that above- mentioned information, which obtain module for obtaining subject's detection information, above-mentioned detection information,
The expression quantity of gene；
Above-mentioned computing module is used to above-mentioned gene involved in immunity expression quantity substituting into prediction model, calculates Risk Score
Value；
Above-mentioned prediction module is used to judge according to above-mentioned Risk Score value the head and neck cancer prognostic risk of above-mentioned subject, such as
The above-mentioned Risk Score value of fruit be less than or equal to predetermined value, then judge above-mentioned subject for head and neck cancer prognosis low-risk person, if
Risk Score value is higher than above-mentioned predetermined value, then judges above-mentioned subject for head and neck cancer prognosis high risk person.
Wherein, head and neck cancer prognosis low-risk person indicates: head and neck cancer patient 2 years, 3 years, 5 years overall survival height, good prognosis.Head
Neck cancer prognosis high risk person indication: head and neck cancer patient 2 years, 3 years, 5 years overall survivals it is low, poor prognosis.
Wherein, above-mentioned gene involved in immunity includes selected from one of following gene or a variety of combinations: RFXAP,
ULBP1、TMSB4Y、RBP4、LCNL1、CCR6、KLRK1、PTX3、MASP1、HRG、CCL22、OLR1、ROBO1、BTC、CHGB、
DKK1, HBEGF, INHBB, PDGFA, AVPR2, IL20RA, RORB, TNFRSF18, TNFRSF25, TNFRSF4, SH3BP2 and
ICOS。
Further, in some embodiments of the present invention, the calculation formula of above-mentioned prediction model is as follows:
F (x)=Sum [Coeffcient × exp],
Wherein, F (x) is Risk Score value, and x is the quantity of gene involved in immunity, and Coeffcient is each immune correlation
The weight coefficient of gene, exp are the high-throughput expression value or small throughput expression value of the mRNA of each gene involved in immunity；
RFXAP、ULBP1、TMSB4Y、RBP4、LCNL1、CCR6、KLRK1、PTX3、MASP1、HRG、CCL22、OLR1、
ROBO1、BTC、CHGB、DKK1、HBEGF、INHBB、PDGFA、AVPR2、IL20RA、RORB、TNFRSF18、TNFRSF25、
The Coeffcient of TNFRSF4, SH3BP2 and ICOS is respectively 0.073,0.007, -0.117,0.067, -0.056, -
0.009、-0.093、0.037、-0.203、0.043、-0.061、0.040、-0.026、0.146、0.113、0.088、0.109、
0.009,0.037,-0.043,-0.067,-0.010,-0.071,-0.051,-0.054,-0.004,-0.017；
Preferably, the calculation formula of the prediction model is as follows:
Risk Score=0.073 × RFXAPexp+0.007 × ULBP1exp-0.117 × TMSB4Yexp+0.067 ×
RBP4exp-0.056×LCNL1exp-0.009×CCR6exp-0.093×KLRK1exp+0.037×PTX3exp-0.203×
MASP1exp+0.043×HRGexp-0.061×CCL22exp+0.04×OLR1exp-0.026×ROBO1exp+0.146×
BTCexp+0.113×CHGBexp+0.088×DKK1exp+0.109×HBEGFexp+0.009×INHBBexp+0.037×
PDGFAexp-0.043×AVPR2exp-0.067×IL20RAexp-0.01×RORBexp-0.071×TNFRSF18exp-
0.051×TNFRSF25exp-0.054×TNFRSF4exp-0.004×SH3BP2exp-0.017×ICOSexp；
Wherein, RFXAPexp, RBP4exp, ULBP1exp, TMSB4Yexp, RBP4exp, LCNL1exp, CCR6exp,
KLRK1exp、PTX3exp、MASP1exp、HRGexp、CCL22exp、OLR1exp、ROBO1exp、BTCexp、CHGBexp、
DKK1exp、HBEGFexp、INHBBexp、PDGFAexp、AVPR2exp、IL20RAexp、RORBexp、TNFRSF18exp、
TNFRSF25exp, TNFRSF4exp, SH3BP2exp, ICOSexp respectively represent RFXAP, RBP4, ULBP1, TMSB4Y, RBP4,
LCNL1、CCR6、KLRK1、PTX3、MASP1、HRG、CCL22、OLR1、ROBO1、BTC、CHGB、DKK1、HBEGF、INHBB、
The high pass of the mRNA of PDGFA, AVPR2, IL20RA, RORB, TNFRSF18, TNFRSF25, TNFRSF4, SH3BP2, ICOS gene
Measure expression value or small throughput expression value.
Further, in some embodiments of the present invention, above-mentioned predetermined value is 0.106.
Further, in some embodiments of the present invention, above-mentioned forecasting system further includes result display module, above-mentioned
Display module is for showing the judging result that above-mentioned prediction module obtains.
Further, in some embodiments of the present invention, the expression quantity of above-mentioned gene involved in immunity uses 2-28
Primer pair detects to obtain；
The base sequence of 2-28 primer pair is successively as follows: SEQ ID NO.3-4, SEQ ID NO.5-6, SEQ ID
NO.7-8、SEQ ID NO.9-10、SEQ ID NO.11-12、SEQ ID NO.13-14、SEQ ID NO.15-16、SEQ ID
NO.17-18、SEQ ID NO.19-20、SEQ ID NO.21-22、SEQ ID NO.23-24、SEQ ID NO.25-26、SEQ
ID NO.27-28、SEQ ID NO.29-30、SEQ ID NO.31-32、SEQ ID NO.33-34、SEQ ID NO.35-36、
SEQ ID NO.37-38、SEQ ID NO.39-40、SEQ ID NO.41-42、SEQ ID NO.43-44、SEQ ID NO.45-
46、SEQ ID NO.47-48、SEQ ID NO.49-50、SEQ ID NO.51-52、SEQ ID NO.53-54、SEQ ID
NO.55-56。
Further, in some embodiments of the present invention, above-mentioned immune phase is detected using above-mentioned 2-28 primer pair
Sample used in the expression quantity of correlation gene is tissue or cell from above-mentioned subject.
5th aspect, the present invention provide a kind of electronic equipment of head and neck cancer prognostic risk prediction, and electronic equipment includes one
Or multiple storage mediums and one or more processors communicated with storage medium, one or more storage mediums are stored with processing
The executable machine-executable instruction of device, when electronic equipment operation, processor executes the machine-executable instruction, to execute
The method of prediction head and neck cancer prognostic risk described in the aforementioned present invention third aspect.
6th aspect, the present invention provide a kind of computer readable storage medium, the computer-readable recording medium storage
There is machine-executable instruction, the machine-executable instruction, which is performed, realizes that prediction head and neck cancer described in the above-mentioned third aspect is pre-
The method of risk afterwards.
Detailed description of the invention
In order to illustrate the technical solution of the embodiments of the present invention more clearly, below will be to needed in the embodiment attached
Figure is briefly described, it should be understood that the following drawings illustrates only certain embodiments of the present invention, therefore is not construed as pair
The restriction of range for those of ordinary skill in the art without creative efforts, can also be according to this
A little attached drawings obtain other relevant attached drawings.
Fig. 1 shows LASSO to choose the gene involved in immunity for head and neck cancer prognosis prediction.
Fig. 2 is the prognostic analysis that head and neck cancer patient is carried out using the immune characteristic genetic model built；Wherein in figure: A,
D indicates the head and neck cancer prognostic model of 27 gene involved in immunity building to two queues of training (A) and validation (D)
Patient carries out distribution (abscissa) sketch map whether risk score (ordinate) and head and neck cancer patient survival；In figure: B, E are indicated
2 queue necks of head and neck cancer prognostic model combination training (B) and validation (E) of 27 gene involved in immunity building
The ROC curve figure of 2 years, 3 years and 5 years follow-up information of cancer patient, area under the curve (Area Under Curve, AUC) explanation
27 gene involved in immunity have good head and neck cancer patient prognosis prediction effect；In figure: C, F indicate 27 gene involved in immunity
The immune high risk group and existence of the low-risk group in two queues of training (C) and validation (F) of model partition
Curve graph, Hazard ratio (hazard ratio, HR) show the high risk group and low-risk group energy that 27 gene involved in immunity divide
Total life span (overall survival, OS) of head and neck cancer patient, P < 0.05 can effectively be divided.
Fig. 3 is the functional block diagram of the head and neck cancer prognostic risk prediction meanss of embodiment 4.
Fig. 4 is the structural block diagram for the electronic equipment that embodiment 5 provides.
Icon: 10- electronic equipment；20- processor；30- memory；40- communication interface；50- bus；100- head and neck cancer is pre-
Risk profile device afterwards；110- data obtaining module；120- computing module；130- prediction module；140- display module.
Specific embodiment
It in order to make the object, technical scheme and advantages of the embodiment of the invention clearer, below will be in the embodiment of the present invention
Technical solution be clearly and completely described.The person that is not specified actual conditions in embodiment, according to normal conditions or manufacturer builds
The condition of view carries out.Reagents or instruments used without specified manufacturer is the conventional production that can be obtained by commercially available purchase
Product.
Feature and performance of the invention are described in further detail with reference to embodiments.
Embodiment 1
Construct prediction model
1. excavating head and neck cancer prognosis gene involved in immunity: using data set in open high throughput TCGA database as opening
Data set is sent out, includes 500 head and neck cancer clinical samples, wherein 499 patients have complete clinical prognosis information.It is immunity-related
Because obtaining from ImmPort database, add up to 1073 genes.Wherein 915 gene involved in immunity are in CIT microarray dataset
In measure, and the expression between different head and neck cancer patients there were significant differences (Median Absolute Deviation,
MAD>0.5).Resampling (resampling) then is carried out, in 1000 resampling, if the variable is selected more than 800
It is secondary, then enter final mask, to obtain 81 candidate genes.
2. the gene involved in immunity building of prediction head and neck cancer prognosis: according to the prognosis information of patient, using LASSO Cox mould
81 gene involved in immunity are reduced to 27 genes, as shown in Figure 1 by type.In addition, immune characteristic genetic model calculation method is adopted
It is multiplied with weighting, F (x)=Sum [Coeffcient (each gene weights coefficient in model) × exp (each gene mRNA table in model
Up to value)].RFXAP,ULBP1,TMSB4Y,RBP4,LCNL1,CCR6,KLRK1,PTX3,MASP1,HRG,CCL22,OLR1,
ROBO1、BTC、CHGB、DKK1、HBEGF、INHBB、PDGFA、AVPR2、IL20RA、RORB、TNFRSF18、TNFRSF25、
The immune value-at-risk Coeffcient of TNFRSF4, SH3BP2 and ICOS is respectively 0.073,0.007, -0.117,0.067, -
0.056、-0.009、-0.093、0.037、-0.203、0.043、-0.061、0.040、-0.026、0.146、0.113、0.088、
0.109,0.009,0.037, -0.043, -0.067, -0.010, -0.071, -0.051, -0.054, -0.004, -0.017, in detail
It is shown in Table 1.
Table 1
3. the foundation of head and neck cancer prognostic model: 27 immune characteristic genes are used, prediction model is established:
Risk Score=0.073 × RFXAPexp+0.007 × ULBP1exp-0.117 × TMSB4Yexp+0.067 ×
RBP4exp-0.056×LCNL1exp-0.009×CCR6exp-0.093×KLRK1exp+0.037×PTX3exp-0.203×
MASP1exp+0.043×HRGexp-0.061×CCL22exp+0.04×OLR1exp-0.026×ROBO1exp+0.146×
BTCexp+0.113×CHGBexp+0.088×DKK1exp+0.109×HBEGFexp+0.009×INHBBexp+0.037×
PDGFAexp-0.043×AVPR2exp-0.067×IL20RAexp-0.01×RORBexp-0.071×TNFRSF18exp-
0.051×TNFRSF25exp-0.054×TNFRSF4exp-0.004×SH3BP2exp-0.017×ICOSexp；
Wherein, RFXAPexp, RBP4exp, ULBP1exp, TMSB4Yexp, RBP4exp, LCNL1exp, CCR6exp,
KLRK1exp、PTX3exp、MASP1exp、HRGexp、CCL22exp、OLR1exp、ROBO1exp、BTCexp、CHGBexp、
DKK1exp、HBEGFexp、INHBBexp、PDGFAexp、AVPR2exp、IL20RAexp、RORBexp、TNFRSF18exp、
TNFRSF25exp, TNFRSF4exp, SH3BP2exp, ICOSexp respectively represent RFXAP, RBP4, ULBP1, TMSB4Y, RBP4,
LCNL1、CCR6、KLRK1、PTX3、MASP1、HRG、CCL22、OLR1、ROBO1、BTC、CHGB、DKK1、HBEGF、INHBB、
The mRNA's of PDGFA, AVPR2, IL20RA, RORB, TNFRSF18, TNFRSF25, TNFRSF4, SH3BP2, ICOSexp gene
High-throughput expression value or small throughput expression value.
High-throughput expression value refers to the mRNA expression of the gene measured by technologies such as RNA sequencing technologies or microarray technologies
Level value, small throughput expression value refer to the mRNA table of the gene measured by technologies such as conventional RT-qPCR or NanoString
Up to level value, value measured by these technologies can substitute into above-mentioned prediction model and be calculated.
The head and neck cancer prognostic risk of subject is judged according to above-mentioned Risk Score value, if Risk Score value be less than or
Equal to 0.106, then subject is judged for head and neck cancer prognosis low-risk person, if Risk Score value is higher than 0.106, in judgement
Stating subject is head and neck cancer prognosis high risk person.
Head and neck cancer prognosis low-risk person indication: head and neck cancer patient 2 years, 3 years, 5 years overall survival height, good prognosis.
Head and neck cancer prognosis high risk person indication: head and neck cancer patient 2 years, 3 years, 5 years overall survivals it is low, poor prognosis.
Experimental example 1
(1 GEO independent data sets, 270 patients, in which: when existence are verified using the sample of known clinical diagnosis result
Between>=there is within 2 years and<3 years 1, life span>=3 year and<5 years have 152, and life span>=5 year have 117) embodiment 1
Prediction model, it was demonstrated that it can significantly predict the prognosis of head and neck cancer patient.Wherein, each gene expression dose of sample used is equal
For high-throughput expression value, it is 0.106 that ROC curve, which divides immune high risk group and the cutoff value of low-risk group,.
Prediction efficiency (see Fig. 2) is as follows: 2 years AUC=0.759,3 years AUC=0.782,5 years AUC in training group (TCGA)
=0.732,2 years specificities 67.5%, 3 years specificities 71%, 5 years specificities 71.8%, sensitivity 72.6% in 2 years, 3 years sensitive
Degree 72.5%, sensitivity 69.2% in 5 years (B in Fig. 2)；2 years AUC=0.578 in validation group (GEO), 3 years AUC=0.611,5 years
AUC=0.719,2 years specificities 62.1%, 3 years specificities 62.7%, 5 years specificities 63.9%, sensitivity 54.2% in 2 years, 3
Year sensitivity 51.9%, sensitivity 52.9% in 5 years (E in Fig. 2).
Experimental example 2
Using a trained queue (TCGA HNSCC), a verifying queue (GSE65858) amounts to 770 clinical samples
In tested.As shown in Fig. 2, wherein the test effect in TCGA data set shows that IRGS is related to OS, low immune risk person
The survival probability of (the Risk Score value<0.106 of IRGS) is high immune risk person (the Risk Score value>0.106 of IRGS)
3.69 times (HR=3.69,95%CI=2.73-4.98, P < 0.001) (C in Fig. 2) of survival probability；In GSE65858
(validation), the low immune risk person related to OS that also show IRGS of the test effect in the head and neck cancer patient of data set
The survival probability of (the Risk Score value<0.106 of IRGS) is high immune risk person (the Risk Score value>0.106 of IRGS)
1.84 times (HR=1.84,95%CI=1.21-2.81, P < 0.01) (F in Fig. 2) of survival probability.
Experimental example 3
Single factor test, the multiplicity of gene involved in immunity models coupling clinic and pathological factor
Table 2 is the results show that in univariate analysis, IRGS (HR=3.69,95%CI=related to the OS in training group
2.73-4.98, P < 0.001, table 2).Similarly, IRGS (HR=1.84,95%CI=1.21- related to the OS in validation group
2.81, P < 0.01, table 2).Even if having adjusted TNM stage factor in multi-variables analysis, IRGS still can be used as only in training group
Independent prediction in vertical predictive factor (HR=3.62,95%CI=2.58-5.09, P < 0.001, table 2), and verifying queue because
Sub (HR=1.73,95%CI=1.12-2.67, P=0.014, table 2).It therefore, really can be with independent prediction using above-mentioned model
Head and neck cancer patient's prognostic risk.
Single factor test, the multiplicity of 2 gene involved in immunity models coupling clinic of table and pathological factor
Embodiment 2
Use the method for the mRNA small throughput expression quantity of real-time fluorescence quantitative PCR detection gene involved in immunity comprising such as
Lower step:
1. the extraction of sample total serum IgE:
(1) 20mg tissue or cell are taken, is added in 2ml Trizol, mixes well, mixed liquor suction is placed in clean nothing
It in the centrifuge tube of RNA enzyme, in sufficiently vibrating 2min on turbula shaker, comes into full contact with tissue with Trizol liquid, mixes, stand
10min draws its supernatant, is placed in the completely centrifuge tube without RNA enzyme.
(2) 15min is centrifuged with 4 DEG C, 12000rpm condition in high-speed refrigerated centrifuge.
(3) chloroform of 1/5 volume of solution in about pipe is added in centrifuge tube, it, will be molten in vibrating 2min on turbula shaker
Liquid is dispensed into the centrifuge tube of new no RNA enzyme, after standing 5min, with 4 DEG C, 12000rpm item in high-speed refrigerated centrifuge
Part is centrifuged 15min.
(4) centrifuge tube is taken out from centrifuge, is drawn upper strata aqueous phase, is placed in the centrifuge tube of no RNA enzyme.
(5) equivalent isopropanol is added in supernatant, mixes well it, after standing 10min, in high-speed refrigerated centrifuge
With 4 DEG C, 12000rpm condition, it is centrifuged 10min.
(6) supernatant is removed, precipitating is retained.Alcohol (75% alcohol) 1ml, Yu Leng diluted using DEPC water is added
Freeze in supercentrifuge with 4 DEG C, 7500rpm condition, is centrifuged 5min.
(7) supernatant is carefully discarded, EP pipe is placed in several minutes of draught cupboard, so that ethyl alcohol thoroughly vapors away, make to precipitate
It is dry.According to the amount of RNA precipitate, 20~40 μ l DEPC are added and handle water, soft piping and druming mixes until RNA is completely dissolved.
2. the preparation of sample cDNA:
The obtained total serum IgE of upper step is subjected to reverse transcription reaction, obtains c DNA.
(1) it is operated, is reacted as follows on ice:
(2) sample is placed on ice, reaction system is as follows:
It mixes, according to 42 DEG C, 60min, 70 DEG C, the condition of 5min carries out reverse transcription reaction, is cooled to 4 DEG C.Later will
CDNA is placed in -20 DEG C of refrigerators and stores.
3. the amplified reaction of fluorescent quantitation
Using GAPDH as internal reference, internal reference and target gene upstream and downstream primer sequence are listed in Table 3 below:
The primer sequence of 3 reference gene of table and target gene
The configuration of PCR reaction system is carried out, reaction system is as follows:
| Reagent | Usage amount |
| SYBR Premix Ex Taq II | 10.0ul |
| PCR forward primer (10u M) | 0.8ul |
| PCR reverse primer (10u M) | 0.8ul |
| C DNA profiling | 2.0ul |
| ROX Reference Dye(50×) | 0.4ul |
| d H2O | 6.0ul |
| Total | 20.0ul |
Each sample sets 2 multiple holes, is added in 8 connecting legs, is detected on 7500 real-time fluorescence quantitative PCR instrument.PCR is followed
Ring condition: 95 DEG C of 30s of initial denaturation are denaturalized 95 DEG C of 5s, and anneal 60 DEG C of 10s, extend 72 DEG C of 15s, recycle 40 times；95 DEG C of 15s are dissolved,
60 DEG C of 1min, 95 DEG C of 15s.
4. interpretation of result: after PCR experiment, checking the amplification situation of each gene, analyze really to solubility curve
Determine whether amplified production is purpose segment.Use 2-ΔΔCtMethod calculate target gene relative expression quantity (ignore fluorescence background,
The target gene situation different from reference gene amplification efficiency, if the oriented parallel illustration purpose gene and internal reference of Exponential growth stage
Gene magnification efficiency is similar).Calculation method: △ Ct=Ct (target gene)-Ct (reference gene), △ △ Ct=△ Ct (experiment
Group)-△ Ct (control group), multiple=2-△△Ct.The obtained multiple of gene involved in immunity i.e. small throughput expression value is substituted into real
It applies and Risk Score can be obtained in the predictor formula in example 1.
Embodiment 3
The present embodiment provides a kind of methods for predicting head and neck cancer prognostic risk comprising following steps:
(1) expression quantity of the following gene involved in immunity of subject is detected:
RFXAP、ULBP1、TMSB4Y、RBP4、LCNL1、CCR6、KLRK1、PTX3、MASP1、HRG、CCL22、OLR1、
ROBO1、BTC、CHGB、DKK1、HBEGF、INHBB、PDGFA、AVPR2、IL20RA、RORB、TNFRSF18、TNFRSF25、
TNFRSF4, SH3BP2 and ICOS.
Wherein, this step detection method used can pass through high-throughput RNA sequencing technologies, microarray technology
(Microarray) etc. it carries out, obtains high-throughput expression value, the real-time quantitative polymerase chain of opposite small throughput can also be passed through
It reacts (RT-qPCR) (such as method provided by embodiment 2) and NanoString technology etc. to carry out, obtains small throughput expression
Value.
It is optional step in step, can be the table for directly obtaining the gene involved in immunity of examination person in other examples
It is calculated up to amount as a result, substituting into subsequent step.
(2) Risk Score value is calculated
The expression quantity for the gene involved in immunity that step (1) obtains is substituted into as drag calculates Risk Score value:
Risk Score=0.073 × RFXAPexp+0.007 × ULBP1exp-0.117 × TMSB4Yexp+0.067 ×
RBP4exp-0.056×LCNL1exp-0.009×CCR6exp-0.093×KLRK1exp+0.037×PTX3exp-0.203×
MASP1exp+0.043×HRGexp-0.061×CCL22exp+0.04×OLR1exp-0.026×ROBO1exp+0.146×
BTCexp+0.113×CHGBexp+0.088×DKK1exp+0.109×HBEGFexp+0.009×INHBBexp+0.037×
PDGFAexp-0.043×AVPR2exp-0.067×IL20RAexp-0.01×RORBexp-0.071×TNFRSF18exp-
0.051×TNFRSF25exp-0.054×TNFRSF4exp-0.004×SH3BP2exp-0.017×ICOSexp。
(3) judgment step
The Risk Score value obtained according to step (2) judges the head and neck cancer prognostic risk of subject, if Risk
Score value is less than or equal to 0.106, then judges subject for head and neck cancer prognosis low-risk person, if Risk Score value is higher than
0.106, then judge subject for head and neck cancer prognosis high risk person.
Head and neck cancer prognosis low-risk person indication: head and neck cancer patient 2 years, 3 years, 5 years overall survival height, good prognosis.
Head and neck cancer prognosis high risk person indication: head and neck cancer patient 2 years, 3 years, 5 years overall survivals it is low, poor prognosis.
Embodiment 4
Head and neck cancer prognostic risk prediction meanss 100 are present embodiments provided, head and neck cancer prognostic risk prediction system is applied to
System.The prediction meanss include: data obtaining module 110, computing module 120, prediction module 130 and display module 140 (with reference to figure
3)。
Wherein, for data obtaining module 110 for obtaining subject's detection information, detection information includes gene involved in immunity
Expression quantity；
Gene involved in immunity include: RFXAP, ULBP1, TMSB4Y, RBP4, LCNL1, CCR6, KLRK1, PTX3, MASP1,
HRG、CCL22、OLR1、ROBO1、BTC、CHGB、DKK1、HBEGF、INHBB、PDGFA、AVPR2、IL20RA、RORB、
TNFRSF18, TNFRSF25, TNFRSF4, SH3BP2 and ICOS.
Computing module 120 is used to above-mentioned gene involved in immunity expression quantity substituting into prediction model, calculates Risk Score
Value；
The calculation formula of prediction model is as follows:
Risk Score=0.073 × RFXAPexp+0.007 × ULBP1exp-0.117 × TMSB4Yexp+0.067 ×
RBP4exp-0.056×LCNL1exp-0.009×CCR6exp-0.093×KLRK1exp+0.037×PTX3exp-0.203×
MASP1exp+0.043×HRGexp-0.061×CCL22exp+0.04×OLR1exp-0.026×ROBO1exp+0.146×
BTCexp+0.113×CHGBexp+0.088×DKK1exp+0.109×HBEGFexp+0.009×INHBBexp+0.037×
PDGFAexp-0.043×AVPR2exp-0.067×IL20RAexp-0.01×RORBexp-0.071×TNFRSF18exp-
0.051×TNFRSF25exp-0.054×TNFRSF4exp-0.004×SH3BP2exp-0.017×ICOSexp；
Wherein, RFXAPexp, RBP4exp, ULBP1exp, TMSB4Yexp, RBP4exp, LCNL1exp, CCR6exp,
KLRK1exp、PTX3exp、MASP1exp、HRGexp、CCL22exp、OLR1exp、ROBO1exp、BTCexp、CHGBexp、
DKK1exp、HBEGFexp、INHBBexp、PDGFAexp、AVPR2exp、IL20RAexp、RORBexp、TNFRSF18exp、
TNFRSF25exp, TNFRSF4exp, SH3BP2exp, ICOSexp respectively represent RFXAP, RBP4, ULBP1, TMSB4Y, RBP4,
LCNL1、CCR6、KLRK1、PTX3、MASP1、HRG、CCL22、OLR1、ROBO1、BTC、CHGB、DKK1、HBEGF、INHBB、
The high pass of the mRNA of PDGFA, AVPR2, IL20RA, RORB, TNFRSF18, TNFRSF25, TNFRSF4, SH3BP2, ICOS gene
Measure expression value or small throughput expression value.
Prediction module 130 is used to judge according to Risk Score value the head and neck cancer prognostic risk of subject, if Risk
Score value is less than or equal to 0.106；Subject is then judged for head and neck cancer prognosis low-risk person, if Risk Score value is higher than
0.106, then judge subject for head and neck cancer prognosis high risk person.
Wherein, head and neck cancer prognosis low-risk person indicates: head and neck cancer patient 2 years, 3 years, 5 years overall survival height, good prognosis.
Head and neck cancer prognosis high risk person indication: head and neck cancer patient 2 years, 3 years, 5 years overall survivals it is low, poor prognosis.
Display module 140 is for showing the judging result that above-mentioned prediction module obtains.
Embodiment 5
A kind of electronic equipment of head and neck cancer prognostic risk prediction is present embodiments provided, with reference to Fig. 4, which includes
Processor 20, communication interface 40, memory 30 and bus 50.
Wherein, processor 20, communication interface 40, memory 30 complete mutual communication, communication interface by bus 50
40 with other equipment for being communicated.Processor 20 is such as implemented for executing the software function module stored in memory 30
The head and neck cancer prognostic risk prediction meanss 100 of example 4.
Processor 20 can be a central processor CPU or specific integrated circuit ASIC (Application
Specifc Integrated Circuit), or be arranged to implement the integrated electricity of one or more of the embodiment of the present application
Road.
Memory 30, for storing computer executable program, memory 30 may include high speed RAM memory, can also
It can further include nonvolatile memory (non-volatile memory), for example, at least a magnetic disk storage.
Wherein, electronic equipment 10 can also be that desktop PC, notebook, palm PC and cloud server etc. calculate
Equipment.It will be understood by those skilled in the art that structure shown in Fig. 4 is merely illustrative, the limit to electronic equipment 10 is not constituted
It is fixed, it may include more or fewer components, perhaps combine certain components or different components, phase can be carried out according to demand
It should be arranged.
Embodiment 6
The present embodiment also provides a kind of computer readable storage medium, which has machine can
It executes instruction, which is performed the side for the head and neck cancer prognostic risk prediction for realizing that above-described embodiment 3 provides
Method.
The foregoing is only a preferred embodiment of the present invention, is not intended to restrict the invention, for the skill of this field
For art personnel, the invention may be variously modified and varied.All within the spirits and principles of the present invention, made any to repair
Change, equivalent replacement, improvement etc., should all be included in the protection scope of the present invention.
SEQUENCE LISTING
<110>ZhongShan University attached No.6 Hospital
<120>application, kit and the head and neck cancer prognostic risk prediction meanss of the reagent of gene involved in immunity expression quantity are detected
<160> 56
<170> PatentIn version 3.5
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Claims (10)
1. application of the reagent of gene involved in immunity expression quantity in the kit of preparation prediction head and neck cancer prognostic risk is detected,
Be characterized in that, the gene involved in immunity is selected from one of following gene or a variety of combinations: RFXAP, ULBP1, TMSB4Y,
RBP4、LCNL1、CCR6、KLRK1、PTX3、MASP1、HRG、CCL22、OLR1、ROBO1、BTC、CHGB、DKK1、HBEGF、
INHBB, PDGFA, AVPR2, IL20RA, RORB, TNFRSF18, TNFRSF25, TNFRSF4, SH3BP2 and ICOS；
Preferably, the gene involved in immunity is selected from one of following gene or a variety of combinations: BTC, CHGB, HBEGF,
DKK1, RFXAP, RBP4, TNFRSF25, TNFRSF4, LCNL1, CCL22, IL20RA, TNFRSF18, KLRK1, TMSB4Y and
MASP1。
2. application according to claim 1, which is characterized in that the reagent is primer, and the primer is selected from 2-28 and draws
Object centering it is one or more；
The base sequence of 2-28 primer pair is successively as follows: SEQ ID NO.3-4, SEQ ID NO.5-6, SEQ ID
NO.7-8、SEQ ID NO.9-10、SEQ ID NO.11-12、SEQ ID NO.13-14、SEQ ID NO.15-16、SEQ ID
NO.17-18、SEQ ID NO.19-20、SEQ ID NO.21-22、SEQ ID NO.23-24、SEQ ID NO.25-26、SEQ
ID NO.27-28、SEQ ID NO.29-30、SEQ ID NO.31-32、SEQ ID NO.33-34、SEQ ID NO.35-36、
SEQ ID NO.37-38、SEQ ID NO.39-40、SEQ ID NO.41-42、SEQ ID NO.43-44、SEQ ID NO.45-
46、SEQ ID NO.47-48、SEQ ID NO.49-50、SEQ ID NO.51-52、SEQ ID NO.53-54、SEQ ID
NO.55-56。
3. a kind of kit for predicting head and neck cancer prognostic risk, which is characterized in that it includes detection gene involved in immunity expression quantity
Reagent, the gene involved in immunity is selected from one of following gene or a variety of combinations: RFXAP, ULBP1, TMSB4Y,
RBP4、LCNL1、CCR6、KLRK1、PTX3、MASP1、HRG、CCL22、OLR1、ROBO1、BTC、CHGB、DKK1、HBEGF、
INHBB, PDGFA, AVPR2, IL20RA, RORB, TNFRSF18, TNFRSF25, TNFRSF4, SH3BP2 and ICOS.
4. kit according to claim 3, which is characterized in that the reagent is primer, and the primer is selected from 2-28
One of primer pair is a variety of；
The base sequence of 2-28 primer pair is successively as follows: SEQ ID NO.3-4, SEQ ID NO.5-6, SEQ ID
NO.7-8、SEQ ID NO.9-10、SEQ ID NO.11-12、SEQ ID NO.13-14、SEQ ID NO.15-16、SEQ ID
NO.17-18、SEQ ID NO.19-20、SEQ ID NO.21-22、SEQ ID NO.23-24、SEQ ID NO.25-26、SEQ
ID NO.27-28、SEQ ID NO.29-30、SEQ ID NO.31-32、SEQ ID NO.33-34、SEQ ID NO.35-36、
SEQ ID NO.37-38、SEQ ID NO.39-40、SEQ ID NO.41-42、SEQ ID NO.43-44、SEQ ID NO.45-
46、SEQ ID NO.47-48、SEQ ID NO.49-50、SEQ ID NO.51-52、SEQ ID NO.53-54、SEQ ID
NO.55-56。
5. a kind of head and neck cancer prognostic risk prediction meanss, which is applied to head and neck cancer prognostic risk forecasting system, and feature exists
In described device includes data obtaining module, computing module and prediction module；
Wherein, for the data obtaining module for obtaining subject's detection information, the detection information includes gene involved in immunity
Expression quantity；
The computing module is used to the expression quantity of the gene involved in immunity substituting into prediction model, to calculate Risk Score
Value；
The prediction module is used to judge according to the Risk Score value head and neck cancer prognostic risk of the subject, if institute
Risk Score value is stated less than or equal to predetermined value, then judges the subject for head and neck cancer prognosis low-risk person, if Risk
Score value is higher than the predetermined value, then judges the subject for head and neck cancer prognosis high risk person；
Wherein, the gene involved in immunity is selected from one of following gene or a variety of combinations: RFXAP, ULBP1, TMSB4Y,
RBP4、LCNL1、CCR6、KLRK1、PTX3、MASP1、HRG、CCL22、OLR1、ROBO1、BTC、CHGB、DKK1、HBEGF、
INHBB, PDGFA, AVPR2, IL20RA, RORB, TNFRSF18, TNFRSF25, TNFRSF4, SH3BP2 and ICOS.
6. head and neck cancer prognostic risk prediction meanss according to claim 5, which is characterized in that the calculating of the prediction model
Formula is as follows:
F (x)=Sum [Coeffcient × exp],
Wherein, F (x) is Risk Score value, and x is the quantity of gene involved in immunity, and Coeffcient is each gene involved in immunity
Weight coefficient, exp be each gene involved in immunity high-throughput expression value or small throughput expression value；
RFXAP、ULBP1、TMSB4Y、RBP4、LCNL1、CCR6、KLRK1、PTX3、MASP1、HRG、CCL22、OLR1、ROBO1、
BTC、CHGB、DKK1、HBEGF、INHBB、PDGFA、AVPR2、IL20RA、RORB、TNFRSF18、TNFRSF25、TNFRSF4、
The Coeffcient of SH3BP2 and ICOS is respectively 0.073,0.007, -0.117,0.067, -0.056, -0.009, -
0.093、0.037、-0.203、0.043、-0.061、0.040、-0.026、0.146、0.113、0.088、0.109、0.009、
0.037,-0.043,-0.067,-0.010,-0.071,-0.051,-0.054,-0.004,-0.017；
Preferably, the calculation formula of the prediction model is as follows:
Risk Score=0.073 × RFXAPexp+0.007 × ULBP1exp-0.117 × TMSB4Yexp+0.067 ×
RBP4exp-0.056×LCNL1exp-0.009×CCR6exp-0.093×KLRK1exp+0.037×PTX3exp-0.203×
MASP1exp+0.043×HRGexp-0.061×CCL22exp+0.04×OLR1exp-0.026×ROBO1exp+0.146×
BTCexp+0.113×CHGBexp+0.088×DKK1exp+0.109×HBEGFexp+0.009×INHBBexp+0.037×
PDGFAexp-0.043×AVPR2exp-0.067×IL20RAexp-0.01×RORBexp-0.071×TNFRSF18exp-
0.051×TNFRSF25exp-0.054×TNFRSF4exp-0.004×SH3BP2exp-0.017×ICOSexp；
Wherein, RFXAPexp, RBP4exp, ULBP1exp, TMSB4Yexp, RBP4exp, LCNL1exp, CCR6exp,
KLRK1exp、PTX3exp、MASP1exp、HRGexp、CCL22exp、OLR1exp、ROBO1exp、BTCexp、CHGBexp、
DKK1exp、HBEGFexp、INHBBexp、PDGFAexp、AVPR2exp、IL20RAexp、RORBexp、TNFRSF18exp、
TNFRSF25exp, TNFRSF4exp, SH3BP2exp, ICOSexp respectively represent RFXAP, RBP4, ULBP1, TMSB4Y, RBP4,
LCNL1、CCR6、KLRK1、PTX3、MASP1、HRG、CCL22、OLR1、ROBO1、BTC、CHGB、DKK1、HBEGF、INHBB、
The high pass of the mRNA of PDGFA, AVPR2, IL20RA, RORB, TNFRSF18, TNFRSF25, TNFRSF4, SH3BP2, ICOS gene
Measure expression value or small throughput expression value.
7. head and neck cancer prognostic risk prediction meanss according to claim 5, which is characterized in that the predetermined value is 0.106.
8. head and neck cancer prognostic risk prediction meanss according to claim 5, which is characterized in that the forecasting system further includes
Result display module, the display module is for showing the judging result that the prediction module obtains.
9. according to the described in any item head and neck cancer prognostic risk prediction meanss of claim 5-8, which is characterized in that the immune phase
The expression quantity of correlation gene detects to obtain using 2-28 primer pair；
The base sequence of 2-28 primer pair is successively as follows: SEQ ID NO.3-4, SEQ ID NO.5-6, SEQ ID
NO.7-8、SEQ ID NO.9-10、SEQ ID NO.11-12、SEQ ID NO.13-14、SEQ ID NO.15-16、SEQ ID
NO.17-18、SEQ ID NO.19-20、SEQ ID NO.21-22、SEQ ID NO.23-24、SEQ ID NO.25-26、SEQ
ID NO.27-28、SEQ ID NO.29-30、SEQ ID NO.31-32、SEQ ID NO.33-34、SEQ ID NO.35-36、
SEQ ID NO.37-38、SEQ ID NO.39-40、SEQ ID NO.41-42、SEQ ID NO.43-44、SEQ ID NO.45-
46、SEQ ID NO.47-48、SEQ ID NO.49-50、SEQ ID NO.51-52、SEQ ID NO.53-54、SEQ ID
NO.55-56。
10. head and neck cancer prognostic risk prediction meanss according to claim 9, which is characterized in that drawn using the 2-28
Object is to the expression quantity for detecting the gene involved in immunity；Sample used is tissue or cell from the subject.
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