CN118150829A - Application of GGT5 as marker in developing product for prognosis of immunotherapy for gastric cancer patient - Google Patents
Application of GGT5 as marker in developing product for prognosis of immunotherapy for gastric cancer patient Download PDFInfo
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Abstract
The invention discloses application of GGT5 serving as a marker in developing a product for prognosis of immunotherapy of gastric cancer patients. The invention provides an application of a substance I or a substance II in preparing a product for prognosis of a gastric cancer patient, an application in preparing a product for predicting the immunotherapy effect of the gastric cancer patient, and an application in preparing a product for histologically grading and/or T-staging gastric cancer tissues. The substance I is an agent or combination of agents for detecting the expression level of GGT5 gene in cancer tissue of a subject. The substance II is a reagent or a reagent combination for detecting the abundance of GGT5 protein in cancer tissues of a subject. The invention has great application and popularization value for clinical diagnosis, immunotherapy and prognosis of gastric cancer.
Description
Technical Field
The invention belongs to the field of medical diagnosis, and relates to application of GGT5 serving as a marker in developing a product for prognosis of immunotherapy for gastric cancer patients. Specifically, the prognosis is a quality of life prognosis or an immune therapy efficacy prognosis.
Background
In recent years, immunotherapy has become a new hope for improving the clinical prognosis of gastric cancer patients. However, since gastric cancer has strong tumor heterogeneity, tumor immune escape events frequently occur, and the immunotherapy effect is limited. According to the results of international large clinical trials CHECKMATE-649: regardless of the PD-L1 Combined Positive Score (CPS), gastric cancer patients receiving the nal Wu Liyou mab combination chemotherapy have better clinical benefit compared to patients receiving chemotherapy alone; the total survival rate (OS) of the combined treatment group for 2 years is close to 40%, the progression-free survival rate (PFS) is obviously improved, and the Objective Remission Rate (ORR) is close to 70%. However, the results of the KEYNOTE-062 test showed that: there was no advantage in receiving immunotherapy in combination with chemotherapy compared to those receiving chemotherapy alone. Thus, the difference in the response of gastric cancer patients to immunotherapy needs to be resolved. It is crucial to study the possible mechanisms and to determine biomarkers that predict the effect of immunotherapy.
Disclosure of Invention
The invention aims to provide application of GGT5 serving as a marker in developing a product for prognosis of immunotherapy for gastric cancer patients.
The invention provides application of a substance I or a substance II in preparation of a product for prognosis of a gastric cancer patient.
The invention also provides application of the substance I or the substance II in preparing a product for predicting the immunotherapy effect of a gastric cancer patient.
The invention also provides application of the substance I or the substance II in preparing a product for histologically grading and/or T-staging stomach cancer tissues.
The substance I is (a 1) or (a 2) as follows:
(a1) An agent for detecting the expression level of a GGT5 gene in a cancer tissue of a subject;
(a2) A combination of reagents for detecting the expression level of a GGT5 gene in cancer tissue of a subject.
The substance II is (b 1) or (b 2) as follows:
(b1) An agent for detecting the abundance of GGT5 protein in a cancer tissue of a subject;
(b2) A combination of reagents for detecting the abundance of GGT5 protein in cancer tissue of a subject.
The subject is a gastric cancer patient.
The invention also provides application of the substance I and a carrier recorded with method A in preparing a product for prognosis of gastric cancer patients;
the method A comprises the following steps:
(1) Detecting GGT5 gene expression levels in cancer tissue of the subject;
(2) Subjects with GGT5 gene expression abundance data greater than or equal to the threshold are at high risk, subjects with GGT5 gene expression abundance data below the threshold are at low risk, and prognosis of low risk is better than high risk;
the subject is a gastric cancer patient.
The invention also provides application of the substance II and a carrier recorded with the method B in preparing a product for prognosis of gastric cancer patients;
the method B comprises the following steps:
(1) Detecting GGT5 protein abundance in cancer tissue of the subject;
(2) The prognosis of the subject with low GGT5 protein abundance is better than that of the subject with high GGT5 protein abundance;
the subject is a gastric cancer patient.
Specifically, the prognosis is a quality of life prognosis or an immune therapy efficacy prognosis.
In particular, the prognosis is a time to live prognosis, a disease-free interval prognosis, a progression-free interval prognosis, or a disease-specific survival prognosis.
Specifically, the prognosis is survival prognosis.
Subjects with GGT5 gene expression abundance data greater than or equal to the threshold are at high risk, subjects with GGT5 gene expression abundance data below the threshold are at low risk, and prognosis for low risk is better than high risk.
The prognosis of subjects with low abundance of GGT5 protein is better than those with high abundance of GGT5 protein.
The prognosis is excellent, and refers to long survival time, long disease-free interval, long progression-free interval or long disease-specific survival time.
The invention also provides application of the substance I and a carrier recorded with a method C in preparing a product for predicting the immunotherapy effect of a gastric cancer patient;
The method C comprises the following steps:
(1) Detecting GGT5 gene expression levels in cancer tissue of the subject;
(2) Subjects with GGT5 gene expression abundance data greater than or equal to the threshold are at high risk, subjects with GGT5 gene expression abundance data below the threshold are at low risk, and the immune effect therapeutic effectiveness of the low risk is higher than the high risk;
the subject is a gastric cancer patient.
The invention also provides application of the substance II and a carrier recorded with the method D in preparing a product for predicting the immunotherapy effect of a gastric cancer patient;
The method comprises the following steps:
(1) Detecting GGT5 protein abundance in cancer tissue of the subject;
(2) Subjects with low abundance of GGT5 protein have a higher therapeutic efficacy for immune effects than subjects with high abundance of GGT5 protein;
the subject is a gastric cancer patient.
The tissue classification of gastric cancer tissue with high GGT5 gene expression abundance is higher than that of gastric cancer tissue with low GGT5 gene expression abundance.
The T-grade of gastric cancer tissue with high GGT5 gene expression abundance is higher than that of gastric cancer tissue with low GGT5 gene expression abundance.
The tissue of gastric cancer tissue with high GGT5 protein abundance has higher histological grade than gastric cancer tissue with low GGT5 protein abundance.
The T grade of gastric cancer tissue with high GGT5 protein abundance is higher than that of gastric cancer tissue with low GGT5 protein abundance.
The invention also provides application of the GGT5 gene or GGT5 protein as a detection marker in developing a product for prognosis of gastric cancer patients.
The invention also provides application of the GGT5 gene or GGT5 protein as a detection marker in developing products for predicting the immunotherapy effect of gastric cancer patients.
The invention also provides application of the GGT5 gene or GGT5 protein as a detection marker in developing products for histologically grading and/or T-staging gastric cancer tissues.
The GGT5 gene expression level of any of the above was obtained by Illumina HiSeq 2000RNA sequencing platform.
Any of the above thresholds (cut off values) is 2.9758.
The abundance of any of the GGT5 proteins described above is obtained by fluorescence immunohistochemistry. In fluorescence immunohistochemistry, GGT5 antibody was used. Specifically, the GGT5 antibody is recombinant Anti-GGT5 antibody [ EPR24682-102], abcam company, product number ab283267. In fluorescence immunohistochemistry, the GGT5 antibody adopts a marker of Opal 570 fluorescence.
The reagent for detecting the abundance of GGT5 protein in cancer tissue of a subject may specifically be: a fluorescent-labeled GGT5 antibody. The fluorescent-labeled GGT5 antibody may specifically be an Opal 570 fluorescent-labeled GGT5 antibody. Specifically, the GGT5 antibody is recombinant Anti-GGT5 antibody [ EPR24682-102], abcam company, product number ab283267.
The invention has great application and popularization value for clinical diagnosis, immunotherapy and prognosis of gastric cancer.
Drawings
FIG. 1 is a box-type diagram of GGT5 gene expression abundance information of 32 cancer tissues and 32 corresponding paracancerous tissues.
FIG. 2 is a Kaplan-Meier curve of Overall Survival (OS) for two risk subgroups.
Fig. 3 is a DCA curve made according to the actual survival of the patient.
FIG. 4 is a Kaplan-Meier curve of DFI for two risk subgroups.
FIG. 5 is a Kaplan-Meier curve of PFI for two risk subgroups.
FIG. 6 is a Kaplan-Meier curve of DSS for two risk subgroups.
FIG. 7 is a box plot of GGT5 expression levels for different histologically graded samples and different T-staged samples.
Fig. 8 is a differential immune cell infiltration ratio between the high risk subgroup and the GGT5 low risk subgroup.
FIG. 9 is a scatter plot of GGT5 gene expression levels correlated with central memory CD8 + T cells and effector memory CD8 + T cells.
FIG. 10 shows the correlation between GGT5 gene expression levels and immune-related genes.
FIG. 11 shows a comparison of TIDE scores between high and low GGT5 expression groups.
FIG. 12 is a violin graph showing the expression levels of GGT5 in different cell types.
FIG. 13 is a photograph of multiple fluorescence immunohistochemistry (mIHC) in example 5.
Detailed Description
The following detailed description of the invention is provided in connection with the accompanying drawings that are presented to illustrate the invention and not to limit the scope thereof. The examples provided below are intended as guidelines for further modifications by one of ordinary skill in the art and are not to be construed as limiting the invention in any way.
The experimental methods in the following examples, unless otherwise specified, are conventional methods, and are carried out according to techniques or conditions described in the literature in the field or according to the product specifications. Materials, reagents and the like used in the examples described below are commercially available unless otherwise specified. Unless otherwise indicated, the quantitative tests in the examples below were all performed in triplicate, and the results averaged. Survival analysis was performed using Kaplan-Meier curve and log rank test. Correlation analysis was performed using Spearman. All statistical analyses were performed using R4.1.3. The differences between the two groups were assessed by the Wilcoxon test. All statistical analyses were bi-directional, p <0.05 indicating statistical significance.
Example 1 discovery of GGT5 Gene expression abundance as a marker
Gene expression profiles of cancer tissue and paracancerous tissue surgically sampled from a gastric cancer patient are obtained. The cancer tissue and the paracancerous tissue of each patient are paired tissues, and the total gene expression profile of the paired tissues is 32 pairs. Gene expression profiles were obtained using the Illumina HiSeq 2000RNA sequencing platform.
According to the gene expression profile, a plurality of differentially expressed genes are initially screened. Further carrying out multi-sample verification on the initially selected genes, and finally finding that GGT5 gene expression abundance can be used as an effective marker for prognosis evaluation of gastric cancer patients.
32 Cancer tissues and corresponding 32 paracancerous tissues were compared for GGT5 gene expression abundance information using the "limma" package and a box-type plot was drawn, see FIG. 1. The expression abundance of GGT5 gene is significantly higher in cancer tissues than in paracancerous tissues.
Data from multiple crowd samples were obtained, and the optimal cut-off value (cut off value) for GGT5 expression abundance was initially determined using the "survivin cutpoint" function of the "survminer" package, and then validated in the multiple crowd samples. The final cut off value was 2.9758.
GGT5 (gamma-glutamyl transferase 5) gene, the species homosapiens (human). Gene ID is: 2687.location is 22q11.23.GENBANK ACCESSION No. NM-004121.5 (30-DEC-2022).
Example 2 grading or prognosis of gastric cancer patients Using GGT5 Gene expression abundance
1. Acquiring relevant data
368 Cases of gastric cancer tissue samples were obtained from gastric cancer tissues collected during surgery of 368 gastric cancer patients.
GGT5 gene expression abundance data (gene expression abundance data obtained by Illumina Hiseq 2000RNA sequencing platform) was obtained for each gastric cancer tissue sample. And according to the cut off value of 2.9758, dividing the patients into two risk subgroups, wherein the patients with GGT5 gene expression abundance data larger than or equal to the cut off value belong to a high risk subgroup, and the patients with GGT5 gene expression abundance data smaller than the cut off value belong to a low risk subgroup.
Subsequent survival data (i.e., time to live from the date of surgery) is obtained for each gastric cancer tissue sample-related patient. And obtaining DFI data, PFI data and DSS data of each gastric cancer tissue sample related patient. And obtaining histological grading data, T grading data and tumor grading data of each stomach cancer tissue sample related patient.
DFI: no disease interval. PFI: no interval of progression. DSS: disease-specific survival.
Specific data information is shown in tables 1 and 2. The patient numbers in table 2 are consistent with the patient numbers in table 1.
TABLE 1
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TABLE 2
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2. Prognosis of survival index using GGT5 gene expression abundance
GGT5 gene expression abundance data of 368 gastric cancer tissue samples, risk subgroup assignment, survival time and survival status of related patients are shown in Table 1. In the survival state, 1 represents that the statistics are dead, and 0 represents that the statistics are fashionable and alive. Time to live refers to the time that the patient survives (in years) from the time of day the surgery began to the time of statistics, with a time to live of 0 being due to the patient's just end of the surgery.
The Kaplan-Meier curves for Overall Survival (OS) for the two risk subgroups are shown in figure 2.Kaplan-Meier curves showed that Gao Weiya groups survived worse than the low-risk subgroup (p=0.0018).
The Gao Weiya groups of patients are predicted to die, the low-risk subgroups of patients are predicted to survive, and DCA curves are generated according to the real survival conditions of the patients, and the results are shown in figure 3. From the graph, the curve distribution of GGT5 is far away from all-none two lines, which shows that the model has good clinical application value and large net benefit.
3. Prognosis of other related indicators using GGT5 gene expression abundance
The DFI, DFI time (in days), PFI time (in days), DSS time (in days) of the partial patients involved in 368 gastric cancer tissue samples are shown in table 2.DFI:1 represents disease recurrence or death, and 0 represents others. PFI:1 represents disease progression or death, and 0 represents others. DSS:1 represents death caused by a disease, and 0 represents death not caused by a disease.
The Kaplan-Meier curves of DFI for two risk subgroups (only counting samples from which DFI data was obtained) are shown in fig. 4. The Kaplan-Meier curves for PFI for the two risk subgroups (statistical only on samples from which PFI data were obtained) are shown in fig. 5. The Kaplan-Meier curves of DSS for two risk subgroups (statistical only on samples from which DSS data were obtained) are shown in fig. 6. The results show that the high risk subgroups DFI (p=0.032), PFI (p=0.0034), DSS (p=9e-04) are all lower risk subgroup differences, i.e. high expression of GGT5 gene is associated with poor clinical prognosis in gastric cancer patients.
4. Identification and classification of abundance of GGT5 gene expression
The GGT5 expression levels of the different histologically graded samples were compared and plotted.
Comparing the GGT5 expression levels of different T-stage samples, and drawing a box-type graph.
The results are shown in FIG. 7. The expression level of GGT5 gene in T3+T4 gastric cancer patients is higher than that in T1+T2 (p=0.018), and the expression level of GGT5 gene in G3 patients is higher than that in G1+G2 (p=2.11e-06). The result shows that the expression level of GGT5 gene in patients with advanced gastric cancer is higher than that in patients with early gastric cancer, which suggests that the GGT5 gene is related to poor clinical prognosis of gastric cancer.
Example 3 Effect of GGT5 on the immune microenvironment of gastric cancer patients
Analysis was performed on the sample data information of example 2.
The expression matrix of 22 immune cells can be deconvolved by CIBERSORT analysis through linear support vector regression, so that the proportion of tumor infiltration immune subpopulations is obtained. Differential immune cell infiltration ratios between the high risk subgroup and the GGT5 low risk subgroup were calculated using cibert, respectively. The results are shown in FIG. 8. The results indicate that there are multiple tumor immune cell infiltrates between the high risk subgroup and the low risk subgroup, wherein: naive B cells (p=0.041), tregs cells (p=0.046), monocytes (p < 0.001) and resting mast cells (p < 0.001) infiltrate at a high risk subset; resting memory CD4 + T cells (p=0.019), activated memory CD4 + T cells (p=0.021), follicular helper T cells (p=0.001) and M0 macrophages (p=0.002) infiltrate at a low rate in the high risk subset. The data indicate that GGT5 can regulate gastric cancer immune microenvironment.
Markers of 28 immune cells were obtained and analyzed ssGSEA to investigate the relationship between these immune cells and GGT5 expression levels and gastric cancer stage. In patients with gastric cancer with high GGT5 expression and advanced tumor, the enrichment degree of memory CD8 + T cells is higher. The correlation of GGT5 gene expression levels with central memory CD8 + T Cells (TCM) and effector memory CD8 + T cells (TEM) was calculated using the "ggpubr" and "ggplot2" packages and a scatter plot was drawn. The results are shown in FIG. 9. The results indicate that there is a strong positive correlation between GGT5 gene expression and TCM (r=0.49, p <2.2 e-16) and TEM (r=0.51, p <2.2 e-16). The data indicate that GGT5 can regulate gastric cancer immune microenvironment by promoting memory CD8 + T cell infiltration.
The correlation of GGT5 gene expression levels with immune related genes (e.g., immune activating genes, immune suppressing genes, inflammatory factor receptor genes) was calculated using the "corrplot" package and plotted. The results are shown in FIG. 10. The results show that GGT5 gene expression is positively correlated with most immune related gene expression, especially immune activating genes and inflammatory factor receptor genes. In conclusion, the GGT5 gene expression level is positively correlated with various immune infiltration cells and immune related genes, which suggests that the GGT5 gene expression level can regulate and control gastric cancer immune microenvironment and participate in gastric cancer immunotherapy.
And predicting the curative effect of GGT5 on gastric cancer immunotherapy by using a TIDE score. The higher the TIDE score, the greater the chance that it will take place for immune escape, the worse the response to Immune Checkpoint Inhibitors (ICIs). The TIDE score of the gastric cancer sample was calculated on the TIDE website (http:// TIDE. Dfci. Harvard. Edu /), and the height of the TIDE score between the high and low expression GGT5 groups was compared. The results are shown in FIG. 11. The results indicate that the higher the GGT5 expression, the higher the TIDE score, suggesting that GGT5 overexpressed patients may be more susceptible to immune escape, resulting in poorer efficacy against immune checkpoint inhibitors.
EXAMPLE 4,
1. Acquisition of Single cell data
10 Cases of gastric cancer tissue samples were obtained from gastric cancer tissues collected during surgery of 10 gastric cancer patients (5 cases of superficial gastric cancer patients, 5 cases of invasive gastric cancer patients). Single cell data of 10 gastric cancer tissue samples were obtained.
2. Single cell data analysis
1. Data processing
The "Seurat" package raw data pair was used for accurate processing. Quality control was performed according to the criteria that ① cells per sample were counted at least 500, and that the proportion of ② mitochondrial gene was less than 5%. Next, s4 data was normalized using NormalizeData functions and the first 2000 hypervariable genes were identified using FindVariableFeatures functions (HVGs). The "SCALEDATA" function is used to further identify, concentrate and scale the selected hypervariable genes. And adopting RunPCA functions to reduce the dimension of the hypervariable genes. Spectral clustering were used to identify different cell clusters. Further clustering was then performed using the functions "FindNeighbors" and "FindClusters", setting the resolution parameter to 0.4, and visualizing the results through t-SNE.
2. Regulation and control of gastric cancer immune microenvironment by GGT5
To cluster different cell types, a "SingleR" package is used to reference the cell type database. The "FINDALLMAKERS" function was then used to screen for the signature gene, with a threshold set at 0.5. The expression levels of GGT5 in different cell types were examined and plotted as violin plots. The results are shown in FIG. 12. The results indicate that GGT5 is significantly enriched in T cells.
T cells were extracted for further analysis. Again, normalizeData, runPCA, findNeighbors and FindClusters functions were used to aggregate the different T cell subtypes and a tSNE cluster analysis was performed showing the expression profile of the T cell subpopulations. The marker genes for each subpopulation of T cells were screened and the identified clusters were re-annotated. The expression levels of GGT5 in all T cell subsets were calculated, and the results showed that GGT5 was highly expressed in the C0-CD8-IL7R, C-CD 8-CCR7 and C8-CD8-TK1 cell clusters, which represent markers (IL 7R, CCR, TK 1) both closely related to CD8+ T cells, in particular memory CD8+ T cells. This result suggests that GGT5 may affect gastric cancer immune microenvironment by affecting memory cd8+ T cells, thereby affecting gastric cancer immunotherapy.
EXAMPLE 5,
10 Cases of gastric cancer tissue samples were obtained from gastric cancer tissues collected during surgery of 10 gastric cancer patients (patient information is shown in table 3, all volunteers with informed consent, all in the department of capital medical university affiliated to the Beijing Korea hospital for immunotherapy).
Each patient was evaluated for response to immunotherapy according to RECIST criteria, and the patients were divided into a partial relief group (PR) group and a non-PR group.
TABLE 3 Table 3
| Age of | Sex (sex) | Immunotherapeutic medicine | Time of first use immunotherapy | Curative effect | |
| Patient 1 | 78 | Female | Nivolumab | 2023/4/18 | PR |
| Patient 2 | 64 | Man's body | Tislelizumab | 2023/4/26 | Non-PR |
| Patient 3 | 53 | Man's body | Tislelizumab | 2023/3/13 | Non-PR |
| Patient 4 | 70 | Man's body | Sintilimab | 2022/8/25 | PR |
| Patient 5 | 64 | Man's body | Tislelizumab | 2022/9/23 | PR |
| Patient 6 | 68 | Man's body | Sintilimab | 2021/11/6 | PR |
| Patient 7 | 63 | Man's body | Sintilimab | 2021/9/28 | Non-PR |
| Patient 8 | 51 | Man's body | Tislelizumab | 2020/5/21 | PR |
| Patient 9 | 39 | Female | Tislelizumab | 2020/7/15 | PR |
| Patient 10 | 76 | Man's body | Sintilimab | 2020/4/30 | PR |
Gastric cancer tissue samples were taken, paraffin sections were made, and then subjected to multiple fluorescence immunohistochemistry (mIHC).
Antibodies used for multiplex fluorescence immunohistochemistry were: GGT5 antibodies, CD45RO antibodies, CD8 antibodies and CCR7 antibodies. GGT5 antibody, designated as recombinant Anti-GGT5 antibody [ EPR24682-102], available from abcam under the trade designation ab283267.CD45RO antibody, which is called Anti-CD45RO antibody [ UCH-L1], abcam company, cat# ab23.CD8 antibody, commonly known as CD8a Monoclonal antibody, proteintech company, under the accession number 66868-1-lg. CCR7 antibody, designated as recombinant Anti-CCR7 antibody [ EPR23192-57], abcam company, cat# ab253187. Multiple fluorescence immunohistochemistry was performed using Opal TM -Color Manual IHC Kit (PERKINELMER, USA) and following the kit instructions. The GGT5 antibody uses the label Opal 570 Fluorophore. The label used for the CD45RO antibody was Opal 520 Fluorophore. The label used for CD8 antibody was Opal 620 Fluorophore. The marker used for CCR7 antibodies was Opal 690 Fluorophore.
Cells positive for all CD8, CD45RO and CCR7 were defined as memory CD8 + T cells. Each channel was captured and analyzed separately using ndp.
The results are shown in FIG. 13 (top-down in FIG. 13, patient numbers 3, 2, 7, 8, 10, 9, 6,1, 5, 4 for each patient). The results indicate that GGT5 gene expression is positively correlated with the degree of memory CD8 + T cell enrichment. In addition, patients from the non-PR group (group 1) exhibited higher levels of GGT5 gene expression abundance and higher concentrations of memory CD8 + T cell enrichment. Thus, mIHC results not only demonstrate a significant correlation between GGT5 and memory cd8+ T cell enrichment, but also demonstrate that patients with high GGT5 expression respond worse to immunotherapy.
The present application is described in detail above. It will be apparent to those skilled in the art that the present application can be practiced in a wide range of equivalent parameters, concentrations, and conditions without departing from the spirit and scope of the application and without undue experimentation. While the application has been described with respect to specific embodiments, it will be appreciated that the application may be further modified. In general, this application is intended to cover any variations, uses, or adaptations of the application following, in general, the principles of the application and including such departures from the present disclosure as come within known or customary practice within the art to which the application pertains. The application of some of the basic features may be done in accordance with the scope of the claims that follow.
Claims (10)
1. Application of substance I or substance II in preparing a product for prognosis of gastric cancer patients;
the substance I is (a 1) or (a 2) as follows:
(a1) An agent for detecting the expression level of a GGT5 gene in a cancer tissue of a subject;
(a2) A combination of reagents for detecting the level of GGT5 gene expression in a cancer tissue of a subject;
the substance II is (b 1) or (b 2) as follows:
(b1) An agent for detecting the abundance of GGT5 protein in a cancer tissue of a subject;
(b2) A combination of reagents for detecting the abundance of GGT5 protein in cancer tissue of a subject.
2. Use of a substance i as claimed in claim 1 and of a carrier describing method a for the preparation of a product for prognosis of patients with gastric cancer;
the method A comprises the following steps:
(1) Detecting GGT5 gene expression levels in cancer tissue of the subject;
(2) Subjects with GGT5 gene expression abundance data greater than or equal to the threshold are at high risk, subjects with GGT5 gene expression abundance data below the threshold are at low risk, and prognosis of low risk is better than high risk;
the subject is a gastric cancer patient.
3. Use of a substance ii as claimed in claim 1 and a carrier describing method b for the preparation of a product for prognosis of a gastric cancer patient;
the method B comprises the following steps:
(1) Detecting GGT5 protein abundance in cancer tissue of the subject;
(2) The prognosis of the subject with low GGT5 protein abundance is better than that of the subject with high GGT5 protein abundance;
the subject is a gastric cancer patient.
4. Use of a substance i as defined in claim 1 or a substance ii as defined in claim 1 for the preparation of a product for predicting the immunotherapeutic effect of a gastric cancer patient.
5. Use of a substance i as defined in claim 1 and a carrier describing method c for the preparation of a product for predicting the immunotherapeutic effect of a patient suffering from gastric cancer;
The method C comprises the following steps:
(1) Detecting GGT5 gene expression levels in cancer tissue of the subject;
(2) Subjects with GGT5 gene expression abundance data greater than or equal to the threshold are at high risk, subjects with GGT5 gene expression abundance data below the threshold are at low risk, and the immune effect therapeutic effectiveness of the low risk is higher than the high risk;
the subject is a gastric cancer patient.
6. Use of a substance ii as claimed in claim 1 and a carrier in which methodological acts are described for the preparation of a product for predicting the immunotherapeutic effect of gastric cancer patients;
The method comprises the following steps:
(1) Detecting GGT5 protein abundance in cancer tissue of the subject;
(2) The immune effect treatment effectiveness of the subjects with low GGT5 protein abundance is superior to that of the subjects with high GGT5 protein abundance;
the subject is a gastric cancer patient.
7. Use of a substance i as defined in claim 1 or a substance ii as defined in claim 1 for the preparation of a product for histological grading and/or T-staging of stomach cancer tissue.
Application of GGT5 gene or GGT5 protein as detection marker in developing prognosis product for gastric cancer patient.
Application of GGT5 gene or GGT5 protein as detection marker in developing product for predicting immunotherapy effect of gastric cancer patient.
Use of GGT5 gene or GGT5 protein as a detection marker for the development of a product for histological classification and/or T-staging of gastric cancer tissue.
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