A system for predicting recurrence of craniopharyngioma based on cdk4 cnv amplification

Abstract

The application discloses a system for predicting recurrence of craniopharyngioma based on CDK4 CNV amplification. In the research on patients with recurrent and ectopic recurrent craniopharyngioma, it is found for the first time that CDK4 gene has a stable copy number gain (CNV) phenomenon, and the proportion of the phenomenon in patients with multiple recurrence is significantly higher than that in patients with initial onset. By detecting the CDK4 CNV amplification condition of tumor tissue blood vessel endothelial cells, the recurrence risk of craniopharyngioma can be evaluated. Therefore, the application provides a craniopharyngioma recurrence risk prediction method, system and device, has good repeatability and popularization potential, can be expanded into a postoperative pathological sample auxiliary diagnosis tool, and realizes stratified evaluation of recurrence risk of postoperative patients and optimization of follow-up strategies.

Description

TECHNICAL FIELD

[0001] The present application relates to the field of intelligent medical treatment, and particularly relates to a system for predicting recurrence of craniopharyngioma based on CDK4 CNV amplification. BACKGROUND

[0002] Craniopharyngioma (CP) is a common intracranial tumor that mainly occurs in children and adolescents. This tumor originates from the epithelial cells of the craniopharyngeal duct and is usually located in the sellar region, closely related to important structures such as the hypothalamus, pituitary stalk, and optic nerve. Postoperative recurrence is an important characteristic of craniopharyngioma, and there is currently a lack of effective means for predicting recurrence. Therefore, developing a method that can effectively predict the recurrence of craniopharyngioma is crucial for patients with craniopharyngioma. SUMMARY

[0003] To make up for the shortcomings of the prior art, the present application provides a system for predicting recurrence of craniopharyngioma based on CDK4 CNV amplification.

[0004] To achieve the above-mentioned purpose, the present application adopts the following technical solutions:

[0005] The first aspect of the present application provides a method for predicting the risk of recurrence of craniopharyngioma, comprising the following steps:

[0006] Obtaining the CNV amplification of genes / proteins in the sample to be tested;

[0007] Extracting the CNV amplification of target genes / proteins in the CNV amplification of genes / proteins, the target genes / proteins including CDK4;

[0008] Based on the CNV amplification of CDK4, the risk of recurrence of craniopharyngioma is predicted, and the classification result of the risk of recurrence of craniopharyngioma in the sample to be tested is obtained; if the CNV amplification ratio of CDK4 is high, the result of high risk of recurrence of craniopharyngioma in the sample to be tested is obtained, and if the CNV amplification ratio of CDK4 is low, the result of low risk of recurrence of craniopharyngioma in the sample to be tested is obtained.

[0009] Further, the CNV amplification ratio of CDK4 is the CNV amplification ratio of CDK4 in vascular endothelial cells.

[0010] Further, the CNV amplification ratio of CDK4 is obtained by image analysis.

[0011] Further, the CDK4 amplification standard is CDK4 / CEP12>2.0 or the presence of clustered CDK4 signal clusters.

[0012] Further, the CNV amplification ratio of CDK4 = CDK4 amplification positive blood vessel number / CD31 positive total blood vessel number.

[0013] Further, the craniopharyngioma recurrence is more than 3 times.

[0014] Further, the threshold of the CNV amplification ratio is 3.7%.

[0015] Further, the craniopharyngioma is selected from the group consisting of adamantinomatous craniopharyngioma.

[0016] The second aspect of the present application provides a craniopharyngioma recurrence risk prediction system, the system comprising:

[0017] An acquisition unit is configured to acquire CNV amplification of genes / proteins in a sample to be tested.

[0018] An extraction unit is configured to extract CNV amplification of target genes / proteins in the CNV amplification of genes / proteins, and the target genes / proteins include CDK4.

[0019] A prediction unit is configured to predict the risk of craniopharyngioma recurrence based on the CNV amplification of CDK4, and obtain a classification result of the risk of craniopharyngioma recurrence in the sample to be tested. If the CNV amplification ratio of CDK4 is high, the result of high risk of craniopharyngioma recurrence in the sample to be tested is obtained, and if the CNV amplification ratio of CDK4 is low, the result of low risk of craniopharyngioma recurrence in the sample to be tested is obtained.

[0020] Further, the CNV amplification ratio of CDK4 is the CNV amplification ratio of CDK4 in vascular endothelial cells.

[0021] Further, the CNV amplification ratio of CDK4 is obtained by image analysis.

[0022] Further, the CDK4 amplification standard is CDK4 / CEP12>2.0 or the presence of clustered CDK4 signal clusters.

[0023] Further, the CNV amplification ratio of CDK4 is CDK4 amplification positive blood vessel number / CD31 positive total blood vessel number.

[0024] Further, the craniopharyngioma recurrence is more than 3 times.

[0025] Further, the threshold of the CNV amplification ratio is 3.7%.

[0026] Further, the craniopharyngioma is selected from the group consisting of adamantinomatous craniopharyngioma.

[0027] The third aspect of the present application provides a craniopharyngioma recurrence risk prediction device, the device comprising:

[0028] A memory is configured to store program instructions.

[0029] The processor is configured to invoke program instructions, when the program instructions are executed, to execute the risk prediction method of the first aspect of the present application.

[0030] Further, the craniopharyngioma is selected from the group consisting of adamantinomatous craniopharyngioma.

[0031] The fourth aspect of the present application provides a computer readable storage medium, which stores a computer program, when the computer program is executed by a processor, the steps of the method of the first aspect of the present application are implemented.

[0032] The fifth aspect of the present application provides a computer program product, which comprises a computer program, when the computer program is executed by a processor, the steps of the method of the first aspect of the present application are implemented.

[0033] The sixth aspect of the present application provides application of a reagent for detecting CDK4 CNV in preparation of a craniopharyngioma recurrence risk prediction product.

[0034] Further, the craniopharyngioma is selected from the group consisting of adamantinomatous craniopharyngioma.

[0035] Further, the reagent comprises a probe for CDK4 CNV and a primer for CDK4 CNV.

[0036] Further, the reagent further comprises a detectable label.

[0037] The seventh aspect of the present application provides a craniopharyngioma recurrence risk prediction product, which comprises a reagent for detecting CDK4 CNV.

[0038] Further, the reagent comprises a probe for CDK4 CNV and a primer for CDK4 CNV.

[0039] Further, the craniopharyngioma is selected from the group consisting of adamantinomatous craniopharyngioma.

[0040] Further, the product comprises a kit and a test paper.

[0041] Further, the kit further comprises a detectable label.

[0042] Further, the detectable label comprises a magnetic bead, a fluorescent dye, a radioactive marker and an enzyme.

[0043] Further, the kit further comprises an instruction manual.

[0044] Further, the kit further comprises a buffer.

[0045] Advantages and beneficial effects of the present application:

[0046] The present application first discovers that CDK4 gene has stable copy number gain (CNV) phenomenon in the study of patients with recurrent and ectopic recurrent craniopharyngioma, and the proportion of this phenomenon in multiple recurrence patients is significantly higher than that in primary patients. By detecting the CDK4 CNV amplification in the tumor tissue vascular endothelial cells, the recurrence risk of craniopharyngioma can be evaluated. Therefore, the present application provides a craniopharyngioma recurrence risk prediction method, system and device, which has good repeatability and popularization potential, can be expanded as a postoperative pathological sample auxiliary diagnosis tool, and realizes the stratified evaluation of postoperative patient recurrence risk and the optimization of follow-up strategy. BRIEF DESCRIPTION OF DRAWINGS

[0047] Figure 1 is a craniopharyngioma recurrence risk prediction method provided by the present application;

[0048] Figure 2 is a craniopharyngioma recurrence risk prediction system provided by the present application;

[0049] Figure 3 is a craniopharyngioma recurrence risk prediction device provided by the present application;

[0050] Figure 4 is a tumor HE staining and tumor peripheral vascular endothelial cell immunohistochemical staining diagram, wherein 4A is an enamel cell type craniopharyngioma HE staining diagram, and 4B is a tumor peripheral vascular endothelial cell strong positive marker expression staining diagram (CD31+(purple fluorescence), DAPI(blue fluorescence) marking tumor epithelial cells);

[0051] Figure 5 is a tumor HE staining and tumor peripheral vascular endothelial cell CDK4-DNA fluorescence in situ hybridization (FISH) staining diagram, wherein 5A is an enamel cell type craniopharyngioma HE staining diagram, and 5B is a tumor peripheral partial vascular endothelial cell CDK4 amplification (red fluorescence, yellow arrow mark) staining diagram, and part of the vascular endothelial CDK4 has no obvious DNA expression amplification (green arrow mark);

[0052] Figure 6 is a recurrence risk assessment diagram based on the proportion of CDK4 CNV amplification blood vessels, wherein 6A is a statistical diagram in which the proportion of CDK4 CNV amplification blood vessels is significantly higher in the multiple recurrence group than in the primary group, and 6B is a ROC curve diagram constructed based on the training group and the verification group. DETAILED DESCRIPTION

[0053] In order for those skilled in the art to better understand the present application, the technical solutions in the embodiments of the present application will be described clearly and completely below in conjunction with the drawings in the embodiments of the present application.

[0054] In some of the flow diagrams described in this specification and the accompanying drawings, multiple operations are described in a particular, sequential order. However, it should be understood that, unless otherwise specifically stated in the specification or in the accompanying drawings, the operations can be executed in any order, or in parallel, and sometimes the sequence of the operations can vary. The sequence of operations, such as 101, 102, etc., is merely an example for distinguishing between different operations, and the sequence of the operations itself is not a limitation for a particular order. In addition, the flow diagrams can include more or fewer operations, and the operations can be executed in sequential order or in parallel. It is noted that the descriptions of "first", "second", etc. in this text are used to distinguish different messages, devices, modules, etc., and do not represent the order of precedence or limit the types of "first" and "second".

[0055] The technical solutions in the embodiments of the present application will be described clearly and completely in the embodiments of the present application in combination with the accompanying drawings. Obviously, the described embodiments are only some of the embodiments of the present application, not all the embodiments. Based on the embodiments in the present application, all other embodiments obtained by those skilled in the art without creative labor are within the scope of protection of the present application.

[0056] Figure 1 It is a kind of craniopharyngioma recurrence risk prediction method provided by the present application schematic diagram, specifically, the method comprises the following steps:

[0057] 101: obtain the CNV amplification of the gene / protein of the sample to be tested.

[0058] 102: extract the CNV amplification of the target gene / protein in the CNV amplification of the gene / protein, the target gene / protein includes CDK4.

[0059] 103: based on the CNV amplification of CDK4, the recurrence risk of craniopharyngioma is predicted, and the classification result of the recurrence risk of craniopharyngioma of the sample to be tested is obtained; if the CNV amplification ratio of CDK4 is high, the result of the recurrence risk of craniopharyngioma of the sample to be tested is obtained, if the CNV amplification ratio of CDK4 is low, the result of the recurrence risk of craniopharyngioma of the sample to be tested is low.

[0060] In some embodiments, CDK4 includes wild type, mutant or fragment thereof. The term encompasses full-length, unprocessed CDK4, any form of CDK4 that results from processing in cells, as well as naturally occurring variants of CDK4 (e.g., splice variants or allelic variants). The term encompasses, for example, human CDK4 as well as CDK4 from any other vertebrate source, including mammals such as primates and rodents (e.g., mice and rats), Gene ID: 1019.

[0061] In some embodiments, the craniopharyngioma comprises adamantinomatous craniopharyngioma, squamous papillary craniopharyngioma.

[0062] In specific embodiments, the craniopharyngioma is selected from the group consisting of adamantinomatous craniopharyngioma.

[0063] The screening and verification process of the target gene / protein CDK4 of the present application is as follows:

[0064] The present application collected 118 paraffin-embedded tissue samples of patients diagnosed with adamantinomatous craniopharyngioma by pathology in the Department of Neurosurgery of Xuanwu Hospital of Capital Medical University from January 2020 to December 2024 after admission and surgery. Excluding 20 samples with poor quality and incomplete follow-up data, 98 samples were finally included in the analysis, including primary (49 cases) and multiple recurrence cases (49 cases). According to the 1:2 ratio, 33 patients were included in the training group (16 multiple recurrences, 17 primary), and 65 patients were included in the validation group (33 multiple recurrences, 32 primary).

[0065] In each sample, the system counted the number of CDK4 CNV amplified blood vessels by image analysis, and calculated the proportion of all blood vessels (blood vessels labeled with CD31+), defined as "CDK4 amplified blood vessel proportion". Then the samples were randomly divided into training and validation groups (1:2), that is, modeling was performed according to the grouping standard of "primary vs multiple recurrence (multiple recurrence defined as more than or equal to 3 times of recurrence)". Figure 4 、 Figure 5 )。

[0066] The ROC curve analysis determined that the optimal segmentation threshold of this proportion for predicting recurrence was 0.03691454 (i.e. 3.7%). When the CDK4 amplified blood vessel proportion of a patient is higher than the threshold, it indicates that the patient has a higher risk of recurrence. This index has good stability in the training group (AUC = 0.78, sensitivity 82%, specificity 69%), and also shows excellent prediction performance in the validation group (AUC = 0.90, 95% CI: 0.82-0.97; sensitivity 88%, specificity 85%, accuracy 86%). In addition, the positive predictive value (PPV) and negative predictive value (NPV) are 74% and 79% in the training group, and 85% and 88% in the validation group, respectively (Table 1). Figure 6

[0067] Table 1 Detailed data information for prediction model construction and validation

[0068]

[0069] In some embodiments, the experimental sample processing and section preparation method comprises:

[0070] ​Tissue source: Paraffin-embedded surgical tissue of adamantinomatous craniopharyngioma (ACP) obtained from clinic.

[0071] Slice thickness: Continuous sections with each 4 pm thickness, numbered as A (for CDK4 / CEP12 FISH) and B (for CD31 immunofluorescence staining) pieces.

[0072] Slide type: Positively charged slides (Superfrost Plus), numbering record to ensure consecutive sections pairing analysis of corresponding areas.

[0073] In some embodiments, the staining method detailed steps include:

[0074] 1. CDK4 / CEP12 FISH staining steps (A piece)

[0075] 1) De-waxing and hydration: 2 times of de-waxing with xylene for 10 minutes each time; 2 minutes of hydration with 100%, 95%, 85%, 75% gradient alcohol, and finally tap water flushing.

[0076] 2) Pretreatment: pepsin digestion solution (Amply, preheated to 37°C), treatment for 10-15 minutes; pure water washing, natural air drying.

[0077] 3) Probe hybridization: add 10 pL of mixed probe (Amply CDK4 (12q14) gene amplification probe) (CDK4: red Cy3; CEP12: green FITC); after covering with a coverslip, in the hybridization instrument: 95°C denaturation for 5 minutes; 37°C hybridization for 16 hours.

[0078] 4) Post-hybridization washing: 0.4x SSC / 0.3% NP-40, 72°C washing for 5 minutes; 2x SSC / 0.1% NP-40, room temperature washing for 1 minute; after air drying, add DAPI (nuclear staining), mounting.

[0079] 2. CD31 immunofluorescence staining steps (B piece)

[0080] 1) De-waxing, hydration and antigen retrieval: same as above de-waxing and hydration; antigen retrieval solution: EDTA buffer (pH 9.0), microwave heating for 10 minutes.

[0081] 2) Blocking and antibody incubation: 5% BSA blocking for 30 minutes; primary antibody: anti-CD31 mouse monoclonal antibody (CST# 3528) (1:100, 4°C overnight); after washing the next day, add fluorescent secondary antibody (Alexa Fluor 620, 1:500, room temperature for 1 hour); DAPI nuclear staining, mounting and keeping away from light.

[0082] In some embodiments, the image acquisition device and parameter method include:

[0083] Microscope platform: Olympus VS200 digital pathology slide scanner or Leica DMi8 confocal system.

[0084] Objective magnification: 40x oil or 63x oil.

[0085] Acquisition channels: DAPI (blue); FITC (CEP12 green); Cy3 (CDK4 red); Alexa Fluor 620 (CD31 purple).

[0086] Slide scanning format: TIFF format export for subsequent image analysis.

[0087] In some embodiments, the image analysis and cell counting software (ImageJ) include:

[0088] Software: ImageJ Fiji 1.53t; manual annotation counting using Cell Counter plugin; distinguishing field area using ROIManager; high-resolution images can be loaded with Bio-Formats Importer plugin.

[0089] Image analysis steps:

[0090] A. CD31 slice image analysis (B slice):

[0091] 1) Open CD31 staining image (Alexa Fluor 620 channel).

[0092] 2) Identify continuous vascular structure (CD31+): purple marker in tubular or elliptical closed loop structure.

[0093] 3) Manually count the number of vascular units (each closed loop structure is considered as 1 blood vessel).

[0094] 4) Count multiple fields (5-10 fields are recommended) on each slice, and average the total number of blood vessels.

[0095] B. CDK4 FISH slice image analysis (A slice):

[0096] 1) Open CDK4 / CEP12 FISH image (activate Cy3 and FITC channels respectively).

[0097] 2) Identify vascular endothelial cell nuclei in the structure control area (according to the morphology of the continuous slice position).

[0098] 3) Count the number of CDK4 signals (red dots) and CEP12 signals (green dots) per endothelial nucleus.

[0099] 4) Determine the CDK4 amplification criteria: CDK4 / CEP12 > 2.0; or presence of clustered CDK4 signals (≥ 6 tight red signals).

[0100] 5) Count the number of blood vessels that meet the above criteria (CDK4 amplification positive blood vessels).

[0101] Proportion calculation formula: CDK4 amplification blood vessel proportion = CDK4 amplification positive blood vessel number / total CD31 positive blood vessel number x 100%.

[0102] In some embodiments, the threshold calculation process includes: based on the recurrence situation (primary vs multiple recurrence, defined as ≥ 3 recurrences), the present application assigns a category label to the sample, and uses the pROC package in R software to construct the receiver operating characteristic curve (ROC curve) to evaluate the predictive performance of "CDK4 amplification blood vessel proportion" in distinguishing between the two groups. To find the best predictive threshold, the present application uses the coords() function and sets the best discrimination standard as the maximization of Youden's index to determine the optimal differentiation threshold to achieve the best balance between sensitivity and specificity. The optimal threshold determined by this method is 0.03691454 (i.e. 3.7%). When the CDK4 amplification blood vessel proportion of a patient is higher than the threshold, it indicates that the patient has a higher risk of recurrence. This threshold is stable in the training group (AUC = 0.78, sensitivity 82%, specificity 69%), and shows better predictive performance in the validation group (AUC = 0.90, sensitivity 88%, specificity 85%).

[0103] In some embodiments, the specific calculation process and code include:

[0104] 1) Sample labeling and grouping

[0105] All cases were grouped according to the number of operations, and a category label was assigned for subsequent ROC analysis (primary group = 0, multiple recurrence group = 1).

[0106] 2) ROC curve construction

[0107] R language v4.3.0 and pROC package were used for analysis, with "CDK4 amplification blood vessel proportion" (continuous variable) as the input variable and recurrence risk (0 or 1) as the classification label. The following code was executed:

[0108] library (pROC)

[0109] roc_obj <- roc(response = group, predictor = cdk4_ratio)

[0110] 3) Threshold determination and optimization

[0111] The cutoff with the best performance is extracted from the ROC curve using the coords() function. The optimization criterion is set to maximize the Youden Index (i.e., Sensitivity + Specificity - 1) to achieve the best balance between sensitivity and specificity:

[0112] opt_threshold <- coords(roc_obj, x = "best", best.method = "youden").

[0113] The final optimal threshold is: CDK4 amplification blood vessel ratio = 0.03691454 (i.e., 3.7%).

[0114] Figure 2 The craniopharyngioma recurrence risk prediction system provided by the present application, specifically, the system comprises:

[0115] The acquisition unit 201 is configured to acquire the CNV amplification of genes / proteins of the sample to be tested.

[0116] The extraction unit 202 is configured to extract the CNV amplification of target genes / proteins in the CNV amplification of genes / proteins, and the target genes / proteins include CDK4.

[0117] The prediction unit 203 is configured to perform craniopharyngioma recurrence risk prediction based on the CNV amplification of CDK4, and obtain a classification result of the craniopharyngioma recurrence risk of the sample to be tested; if the CNV amplification ratio of CDK4 is high, a result of high craniopharyngioma recurrence risk of the sample to be tested is obtained, and if the CNV amplification ratio of CDK4 is low, a result of low craniopharyngioma recurrence risk of the sample to be tested is obtained.

[0118] Figure 3 The craniopharyngioma recurrence risk prediction device provided by the present application, specifically, the device comprises:

[0119] The memory is configured to store program instructions.

[0120] The processor is configured to invoke the program instructions, and when the program instructions are executed, the processor is configured to perform the craniopharyngioma recurrence risk prediction method.

[0121] This invention provides a product for predicting the recurrence risk of craniopharyngioma, the product comprising a reagent for detecting CDK4 CNV.

[0122] The reagents include a CDK4 CNV probe and CDK4 CNV primers.

[0123] In some embodiments, primers and amplification primers are used interchangeably. A primer is an oligonucleotide that hybridizes with the target nucleic acid or its complement and participates in the nucleic acid amplification reaction. The amplification primer hybridizes with the template nucleic acid and has a 3'-OH (3'-hydroxyl) group that can be extended by polymerization. In some embodiments, the amplification primer is 15-60, 15-55, 15-50, 15-45, 15-40, 15-35, or 15-30 bases in length. In some embodiments, the amplification primer is 18-30 bases in length. In some embodiments, the amplification primer is 18-60 bases in length and contains 18-30 consecutive bases (target hybridization region) that hybridize with a corresponding 18-30 nucleotide oligonucleotide hybridization sequence present in the target nucleic acid sequence. In some embodiments, the 18-30 consecutive bases are located at the 3' end of the amplification primer.

[0124] In some implementations, a probe refers to an oligonucleotide capable of hybridizing to a target nucleic acid of interest. Depending on the stringency of the hybridization conditions, the probe will typically essentially form a chemical bond between the probe sequence and a target sequence lacking complete complementarity. The probe may be associated with an appropriate tag or reporter moiety so that the probe (and its target) can be detected, visually inspected, measured, and / or determined.

[0125] The products include reagent kits and test strips.

[0126] The kit also includes detectable markers.

[0127] In some implementations, suitable detectable markers include, but are not limited to, magnetic beads (e.g., Dynabeads™), fluorescent dyes (e.g., fluorescein isothiocyanate, Texas red, rhodamine, green fluorescent protein, red fluorescent protein, yellow fluorescent protein, etc.), and radioactive markers (e.g. 3 H, 125 I, 35 S, 14 C, or 32 P), enzymes (such as horseradish peroxidase, alkaline phosphatase, luciferase, and other substances commonly used in enzyme-linked immunosorbent assays (ELISA), and colorimetric markers, such as colloidal gold or colored glass or plastic beads (e.g., polystyrene, polypropylene, latex, etc.).

[0128] In some embodiments, a kit refers to any delivery system for delivering materials. In the context of nucleic acid purification systems and reaction assays, such delivery systems include systems that allow for the storage, transport, or delivery of reagents and devices (e.g., lytic salts, particles, buffers, denaturants, oligonucleotides, filters, etc. in appropriate containers) and / or supporting materials (e.g., sample processing or sample storage containers, written instructions for performing a procedure, etc.) from one location to another. For example, a kit includes one or more enclosures (e.g., boxes) containing the relevant reaction reagents and / or supporting materials.

[0129] In some embodiments, a kit includes a fragmentation kit and a combination kit. A fragmentation kit refers to a delivery system comprising two or more separate containers, each containing a sub-portion of the total kit components. The containers can be delivered together or separately to an intended recipient. For example, a first container can contain materials and buffers for sample collection, while a second container contains capture oligonucleotides and denaturants. A combination kit refers to a delivery system comprising all components of a reaction assay in a single container (e.g., in a single box containing each of the required components).

[0130] In several embodiments provided in the present application, it should be understood that the disclosed system, apparatus, and method can be implemented in other manners. For example, the apparatus embodiments described above are merely schematic. For example, the division of the units is only a logical function division. For another example, a plurality of units or components can be combined or integrated into another system, or some features can be ignored or not executed. In addition, the displayed or discussed mutual couplings or direct couplings or communication connections can be indirect couplings or communication connections through some interfaces, devices, or units, and can be in electrical, mechanical, or other forms.

[0131] The units described as separate components may or may not be physically separate, and the components shown as units may or may not be physical units, i.e., may be located in one place, or may be distributed on a plurality of network units. Some or all of the units can be selected according to actual needs to achieve the purposes of the embodiments.

[0132] In addition, each functional unit in each embodiment of the present application can be integrated into a processing unit, or each unit can exist physically, or two or more units can be integrated into one unit. The integrated unit can be implemented in the form of hardware or in the form of a software functional unit.

[0133] Those skilled in the art can understand that all or part of the steps of the various methods of the above embodiments can be completed by programs instructing relevant hardware, and the programs can be stored in a computer readable storage medium, which can include a read only memory (ROM), a random access memory (RAM), a magnetic disk or an optical disk, etc.

[0134] Those skilled in the art can understand that all or part of the steps of the above embodiments can be completed by programs instructing relevant hardware, and the programs can be stored in a computer readable storage medium, which can include a read only memory (ROM), a random access memory (RAM), a magnetic disk or an optical disk, etc.

[0135] The above description of the embodiments is only for understanding the method of the present application and its core idea. It should be pointed out that, for those skilled in the art, without departing from the principles of the present application, the present application can be improved and modified in several ways, and these improvements and modifications will also fall within the protection scope of the claims of the present application.

Claims

1. A craniopharyngioma recurrence risk prediction system, characterized by, The system comprises: an acquisition unit configured to acquire CNV amplification of genes of a sample to be tested; an extraction unit configured to extract CNV amplification of target genes in the CNV amplification of the genes, the target genes comprising CDK4; a prediction unit configured to predict a recurrence risk of craniopharyngioma based on the CNV amplification of the CDK4 to obtain a classification result of a high or low recurrence risk of craniopharyngioma of the sample to be tested; if the CNV amplification ratio of the CDK4 is high, a result of a high recurrence risk of craniopharyngioma of the sample to be tested is obtained, and if the CNV amplification ratio of the CDK4 is low, a result of a low recurrence risk of craniopharyngioma of the sample to be tested is obtained; the CNV amplification ratio of the CDK4 is a CNV amplification ratio of CDK4 in vascular endothelial cells; a CDK4 amplification standard is CDK4 / CEP12>2.0 or there is a clustered CDK4 signal cluster; the CNV amplification ratio of the CDK4=CDK4 amplification positive blood vessel number / CD31 positive total blood vessel number; the sample to be tested is selected from a tissue.

2. The system of claim 1, wherein, The CNV amplification ratio of the CDK4 is counted by image analysis.

3. The system of claim 1, wherein, The recurrence of the craniopharyngioma is more than 3 times of recurrence of the craniopharyngioma.

4. The system of claim 1, wherein, The threshold value of the CNV amplification ratio is 3.7%.

5. The system of claim 1, wherein, The craniopharyngioma is selected from an enamel cell type craniopharyngioma.

6. A device for predicting a recurrence risk of craniopharyngioma, characterized by The device comprises: a memory configured to store program instructions; a processor configured to invoke the program instructions, when the program instructions are executed, to perform the following method: acquire CNV amplification of genes of a sample to be tested; extract CNV amplification of target genes in the CNV amplification of the genes, the target genes comprising CDK4; predict a recurrence risk of craniopharyngioma based on the CNV amplification of the CDK4 to obtain a classification result of a high or low recurrence risk of craniopharyngioma of the sample to be tested; if the CNV amplification ratio of the CDK4 is high, a result of a high recurrence risk of craniopharyngioma of the sample to be tested is obtained, and if the CNV amplification ratio of the CDK4 is low, a result of a low recurrence risk of craniopharyngioma of the sample to be tested is obtained; the CNV amplification ratio of the CDK4 is a CNV amplification ratio of CDK4 in vascular endothelial cells; a CDK4 amplification standard is CDK4 / CEP12>2.0 or there is a clustered CDK4 signal cluster; the CNV amplification ratio of the CDK4=CDK4 amplification positive blood vessel number / CD31 positive total blood vessel number; the sample to be tested is selected from a tissue.

7. The apparatus of claim 6, wherein, The CNV amplification ratio of the CDK4 is counted by image analysis.

8. The apparatus of claim 6, wherein, The recurrence of the craniopharyngioma is more than 3 times of recurrence of the craniopharyngioma.

9. The apparatus of claim 6, wherein, The threshold value of the CNV amplification ratio is 3.7%.

10. The apparatus of claim 6, wherein, The craniopharyngioma is selected from an enamel cell type craniopharyngioma.

11. A computer readable storage medium, characterized in that, A computer program is stored thereon, and steps of the following method are realized when the computer program is executed by a processor: acquire CNV amplification of genes of a sample to be tested; extract CNV amplification of target genes in the CNV amplification of the genes, the target genes comprising CDK4; predict a recurrence risk of craniopharyngioma based on the CNV amplification of the CDK4 to obtain a classification result of a high or low recurrence risk of craniopharyngioma of the sample to be tested; If the CNV amplification ratio of CDK4 is high, a result that the craniopharyngioma of the test sample has a high risk of recurrence is obtained, and if the CNV amplification ratio of CDK4 is low, a result that the craniopharyngioma of the test sample has a low risk of recurrence is obtained. The CNV amplification ratio of CDK4 is the CNV amplification ratio of CDK4 in vascular endothelial cells. The CDK4 amplification standard is CDK4 / CEP12>2.0 or the presence of clustered CDK4 signal clusters. The CNV amplification ratio of CDK4=number of CDK4 amplification positive blood vessels / total number of CD31 positive blood vessels. The test sample is selected from tissues.

12. The computer-readable storage medium of claim 11, wherein, The CNV amplification ratio of CDK4 is counted by image analysis.

13. The computer-readable storage medium of claim 11, wherein, The craniopharyngioma recurrence is more than 3 times of craniopharyngioma recurrence.

14. The computer-readable storage medium of claim 11, wherein, The threshold value of the CNV amplification ratio is 3.7%.

15. The computer-readable storage medium of claim 11, wherein, The craniopharyngioma is selected from enamel cell type craniopharyngioma.

16. A computer program product comprising a computer program, characterized in that, The computer program is executed by the processor to realize the steps of the following method: Obtain the CNV amplification of the gene of the test sample; Extract the CNV amplification of the target gene in the CNV amplification of the gene, and the target gene includes CDK4; Based on the CNV amplification of CDK4, the risk of craniopharyngioma recurrence is predicted, and the classification result of the test sample craniopharyngioma recurrence risk is obtained. If the CNV amplification ratio of CDK4 is high, a result that the craniopharyngioma of the test sample has a high risk of recurrence is obtained, and if the CNV amplification ratio of CDK4 is low, a result that the craniopharyngioma of the test sample has a low risk of recurrence is obtained. The CNV amplification ratio of CDK4 is the CNV amplification ratio of CDK4 in vascular endothelial cells. The CDK4 amplification standard is CDK4 / CEP12>2.0 or the presence of clustered CDK4 signal clusters. The CNV amplification ratio of CDK4=number of CDK4 amplification positive blood vessels / total number of CD31 positive blood vessels. The test sample is selected from tissues.

17. The computer program product of claim 16, wherein, The CNV amplification ratio of CDK4 is counted by image analysis.

18. The computer program product of claim 16, wherein, The craniopharyngioma recurrence is more than 3 times of craniopharyngioma recurrence.

19. The computer program product of claim 16, wherein, The threshold value of the CNV amplification ratio is 3.7%.

20. The computer program product of claim 16, wherein, The craniopharyngioma is selected from enamel cell type craniopharyngioma.

21. The reagent for detecting the CNV amplification ratio of CDK4 is used for preparing a product for predicting the risk of craniopharyngioma recurrence. The CNV of CDK4 is the CNV amplification ratio of CDK4 in vascular endothelial cells. The CDK4 amplification standard is CDK4 / CEP12>2.0 or the presence of clustered CDK4 signal clusters. The CNV amplification ratio of CDK4=number of CDK4 amplification positive blood vessels / total number of CD31 positive blood vessels. The sample detected by the reagent is selected from tissues.

22. The use according to claim 21, characterized in that, The craniopharyngioma is selected from enamel cell type craniopharyngioma.

23. The use according to claim 21, characterized in that, The reagent includes a probe for CDK4 CNV and a primer for CDK4 CNV.

24. The use according to claim 23, characterized in that, The reagent further includes a detectable label.

25. The use according to claim 21, characterized in that, The product includes a kit and a test paper.

26. The use according to claim 25, characterized in that, The kit further includes a detectable label.

27. The use according to claim 26, characterized in that, The detectable label includes magnetic beads, fluorescent dye, radioactive marker and enzyme.

28. The use of claim 25, wherein, The kit further includes an instruction.

29. The use of claim 25, wherein, The kit further includes a buffer.

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