CN117233391A - Biomarker for predicting curative effect of gastric cancer immunotherapy and/or chemotherapy and application thereof - Google Patents
Biomarker for predicting curative effect of gastric cancer immunotherapy and/or chemotherapy and application thereof Download PDFInfo
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Abstract
The invention discloses a biomarker for predicting the curative effect of immunotherapy and/or chemotherapy of gastric cancer and application thereof; the markers include nicotinamide and N-methylnicotinamide; the invention provides the negative correlation effect of two metabolites of nicotinamide and N-methyl nicotinamide in predicting the immunotherapy efficacy and/or chemotherapy of gastric cancer for the first time, wherein the nicotinamide is related to good immunotherapy and/or chemotherapy response, and the N-methyl nicotinamide is related to poor immunotherapy and/or chemotherapy response; the ratio of nicotinamide/N-methylnicotinamide can be a novel metabolic marker for monitoring gastric cancer immunotherapy. The micro-environmental metabolic intervention based on nicotinamide metabolic heterogeneity can provide application basis for precisely improving gastric cancer immunotherapy and/or chemotherapy strategies; provides a new application direction for the future development of metabonomics based on liquid biopsy.
Description
Technical Field
The invention belongs to the technical field of biological medicines, and particularly relates to a biomarker for predicting curative effects of immunotherapy and/or chemotherapy of gastric cancer and application thereof.
Background
Gastric cancer is a global malignant tumor disease. Successive successes of clinical studies such as clinical study Checkmate-649 and ORIENT-16 in stage III establish that chemoimmune combination becomes a new marker post for the first-line treatment of advanced gastric cancer and also bring gastric cancer to the era of immunotherapy. However, gastric cancer immunotherapy still faces two major challenges. The first is that the curative effect is not ideal: the effective rate of the existing gastric cancer patients receiving single-drug immune checkpoint inhibitor treatment is only 10-25%, the effective rate of the immune checkpoint inhibitor combined chemotherapy is about 40-60%, and the identification of inherent resistance factors of immune treatment is an important link. Second is the decision difficulty: how to select a proper treatment scheme in the treatment process and select potential benefited people and treatment time is a core topic of accurate immunotherapy of gastric cancer.
Currently, MSI/MMR status, PD-L1 expression, tumor Mutational Burden (TMB) and EBV status are common biomarkers for gastric cancer immunotherapy. Among them, the use of immune checkpoint inhibitors for microsatellite high instability (MSI-H) patients has been a clinical consensus; in addition, high TMB, EBV positivity is also associated with better immunotherapeutic response. Recent research and exploration has presented new challenges to the clinical status of the above markers. For example, in the CheckMate-649 study, anti-PD-1 na Wu Liyou mAb combination chemotherapy did not benefit from OS and PFS in CPS 1-4 populations, resulting in a reconsideration of PD-L1 index application. Therefore, under the existing immune biomarker pattern, the development of stable biomarkers is a problem to be solved in order to overcome the dilemma of gastric cancer immunotherapy.
The metabolic microenvironment is an important "regulator" of the immune cycle and is also an important aspect in establishing an evaluation or prediction system. For example, in recent years, a lipid metabolism gene gastric cancer risk model, a metabolic marker, and gastric cancer typing based on glycolysis related genes are reported to predict total survival rate, and a new research direction is proposed for revealing the relationship between gastric cancer metabolic characteristics and immunotherapy. In addition to metabolic pathways, metabolites are mediators that act directly on tumor cells and microenvironment cells, thereby affecting the therapeutic efficacy of immunotherapy. However, the mere use of metabolic inhibitors, while blocking metabolic pathways, makes it difficult to control the dynamic balance between metabolites. Therefore, the metabolic markers are screened on the basis of fully considering the metabolite conversion relation, which is helpful for layering patients and accurately predicting the immune therapy response.
The invention utilizes transcriptome data of gastric cancer samples to score the activity of metabolites, and screens out metabolic molecule pairs with obvious scoring differences among patients responding to different immunotherapy by taking the best immune therapy response and death event as the outcome. Meanwhile, carrying out systematic correlation analysis on the activity of the metabolite, immune cells and immune channel activity, and identifying potential metabolites with immune regulation and control effects; the guiding value of the novel nicotinamide/N-methylnicotinamide metabolic marker in the immune therapy response is initially explored, and the novel application direction is hopeful to be provided for the future development of the liquid biopsy-based metabonomics.
Disclosure of Invention
The object of the first aspect of the present invention is to provide a marker for predicting the efficacy of tumour immunotherapy and/or chemotherapy.
The object of the second aspect of the present invention is to provide a detection reagent.
In a third aspect, the present invention provides the use of a marker or a detection reagent as described above.
The object of the fourth aspect of the invention is to provide a product.
A fifth aspect of the present invention is directed to a detection system.
A sixth aspect of the present invention is directed to a computer-readable storage medium.
The technical scheme adopted by the invention is as follows:
in a first aspect of the invention there is provided a marker for predicting the efficacy of tumour immunotherapy and/or chemotherapy comprising nicotinamide and N-methylnicotinamide.
Preferably, the efficacy of tumour immunotherapy and/or chemotherapy is predicted by calculating the ratio of nicotinamide and N-methylnicotinamide content.
Preferably, the present invention selects patients on which immunotherapy is the primary screening condition, and also focuses on analyzing the microenvironment associated with bias immunity, so that the immunotherapy and/or chemotherapy is based on immunotherapy, specifically comprising: prediction of efficacy of two treatment modalities, immunotherapy and chemotherapy.
Preferably, if the ratio of nicotinamide to N-methylnicotinamide is significantly higher than before treatment, immunotherapy and/or chemotherapy is effective for its treatment; if the ratio of nicotinamide to N-methylnicotinamide is significantly lower than before treatment, the immunotherapy and/or chemotherapy has no or insignificant therapeutic effect on it.
Preferably, the chemotherapeutic agent comprises at least one of 5-fluorouracil, a taxoid, platinum, and ifenprodil Li Tikang.
Preferably, the paclitaxel includes, but is not limited to, at least one of paclitaxel, docetaxel, albumin paclitaxel, paclitaxel liposome.
Preferably, the platinum group includes, but is not limited to, at least one of cisplatin, carboplatin, oxaliplatin, nedaplatin, lobaplatin.
Preferably, the immunotherapy comprises treatment with an immune checkpoint inhibitor.
Preferably, the immune checkpoint inhibitor includes, but is not limited to, at least one of a PD-1 antibody, a PD-L1 antibody, CTLA-4.
Preferably, the neoplasm includes benign neoplasm and malignant neoplasm, including, but not limited to, intestinal cancer, lung cancer, melanoma, gastric cancer, squamous cell carcinoma, fibroma, pancreatic cancer, lipoma, vascular endothelial tumor, osteosarcoma, glomeruloma, osteoma, giant cell tumor, meningioma, lymphoma, thyroid cancer, liver cancer, ovarian cancer, head and neck cancer, breast cancer, cervical cancer, renal cancer, bladder cancer, prostate cancer, esophageal cancer, ovarian cancer, and cholangiocarcinoma.
Preferably, the tumor is gastric cancer.
In a second aspect of the invention, there is provided a detection reagent comprising reagents for quantitatively detecting the levels of nicotinamide and N-methylnicotinamide according to the first aspect of the invention.
Preferably, the detection reagent comprises a reagent for detecting nicotinamide and N-methylnicotinamide content by at least one of an enzyme-linked immunosorbent assay (ELISA), western blot, radioimmunoassay, immunohistochemical staining kit, immunoprecipitation assay kit, complement fixation assay kit, microarray and protein chip.
Preferably, the detection reagent comprises an antibody.
Preferably, the sample to be tested is at least one selected from the group consisting of tissue, cells, peripheral blood, plasma, serum, blood, urine, tears and fluids collected by bronchial lavage and/or peritoneal irrigation.
In a third aspect, the invention provides the use of a marker according to the first aspect of the invention or a detection reagent according to the second aspect of the invention in the manufacture of a product for predicting the efficacy of tumour immunotherapy and/or chemotherapy.
Preferably, the product comprises reagents, test papers, kits and chips.
In a fourth aspect of the invention, there is provided a product comprising a detection reagent according to the second aspect of the invention.
Preferably, the method of using the product comprises:
s1: detecting the content of nicotinamide and N-methylnicotinamide in a sample to be detected;
s2: calculating the ratio of nicotinamide to N-methylnicotinamide according to the content of nicotinamide and N-methylnicotinamide, and predicting the curative effect of immunotherapy and/or chemotherapy according to the ratio of nicotinamide to N-methylnicotinamide.
If the ratio of nicotinamide to N-methylnicotinamide is significantly higher than before treatment, immunotherapy and/or chemotherapy is effective for the treatment of the subject; if the ratio of nicotinamide to N-methylnicotinamide is significantly lower than before treatment, the immunotherapy and/or chemotherapy has no or insignificant therapeutic effect on the subject.
In a fifth aspect of the present invention, there is provided a detection system comprising:
a detection device for determining the nicotinamide and N-methylnicotinamide content in a sample of a subject;
and the analysis device is used for obtaining the detection result, calculating the ratio of nicotinamide to N-methylnicotinamide, and predicting the curative effect of immunotherapy and/or chemotherapy according to the ratio of nicotinamide to N-methylnicotinamide.
If the ratio of nicotinamide to N-methylnicotinamide is significantly higher than before treatment, immunotherapy and/or chemotherapy is effective for the treatment of the subject; if the ratio of nicotinamide to N-methylnicotinamide is significantly lower than before treatment, the immunotherapy and/or chemotherapy has no or insignificant therapeutic effect on the subject.
In a sixth aspect of the invention, a computer readable storage medium is provided, storing a computer program, which when executed by a processor, performs the functions of the system according to the fifth aspect of the invention.
The beneficial effects of the invention are as follows:
the invention provides the negative correlation effect of two metabolites of nicotinamide/N-methylnicotinamide in predicting the curative effect of immunotherapy and/or chemotherapy of gastric cancer for the first time, wherein nicotinamide is related to good immunotherapy and/or chemotherapy response, and N-methylnicotinamide is related to poor immunotherapy and/or chemotherapy response; the ratio of nicotinamide/N-methylnicotinamide can be a novel metabolic marker for monitoring the immunotherapy and/or chemotherapy of gastric cancer. The micro-environmental metabolic intervention based on nicotinamide metabolic heterogeneity can provide application basis for precisely improving gastric cancer immunotherapy and/or chemotherapy strategies; provides a new application direction for the future development of metabonomics based on liquid biopsy.
Drawings
Fig. 1 is a general flow chart of the present invention.
FIG. 2 shows the immune-related scores of pairs of metabolic antagonistic molecules, and red labeled nicotinamide/N-methylnicotinamide pairs.
FIG. 3 is a thermal graph of metabolic antagonistic molecules versus immune cell correlation, C00153: nicotinamide, C02918: n-methylnicotinamide.
FIG. 4 is a heat map of the correlation of nicotinamide metabolism antagonistic molecules to 25 immune cells, NAM: nicotinamide, MNAM: n-methylnicotinamide.
FIG. 5 shows the nicotinamide/N-methylnicotinamide ratio in peripheral blood of gastric cancer patients receiving immunotherapy. Fig. 5A is a ratio of nicotinamide/N-methylnicotinamide in peripheral blood of treatment-responsive group patients (PR, n=16) and non-responsive group (SD/PD, n=62); FIG. 5B is a graph showing the ratio of nicotinamide to N-methylnicotinamide in peripheral blood paired before and after immunotherapy in treatment-responsive patients; FIG. 5C is a graph showing the nicotinamide/N-methylnicotinamide ratio in paired peripheral blood of non-responsive patient samples before and after immunotherapy.
FIG. 6 is a graph showing the trend of peripheral blood nicotinamide/N-methylnicotinamide ratio at different treatment nodes for 3 typical gastric cancer patients. The time line of FIG. 6 is the sampling time, with Patents A-C representing 3 patients.
Fig. 7 is an image representation of 3 exemplary gastric cancer patients at different treatment nodes. Noted under the horizontal arrow in fig. 7 is the treatment regimen used for this period of time, with Patient a-C representing 3 patients.
Detailed Description
The conception and the technical effects produced by the present invention will be clearly and completely described in conjunction with the embodiments below to fully understand the objects, features and effects of the present invention. It is apparent that the described embodiments are only some embodiments of the present invention, but not all embodiments, and that other embodiments obtained by those skilled in the art without inventive effort are within the scope of the present invention based on the embodiments of the present invention.
The general flow chart of the invention is shown in fig. 1, comprising:
downloading transcriptome sequencing data and corresponding clinical pathology information of clinical samples of gastric cancer patients in a public database (GSE 62254/PRJEB 25780);
based on metabolite-protein interaction information published by Chen et al (PMID: 34247449), a metabolite gene set was organized, and each metabolite score of the patient was obtained using the metabolite gene set by means of the "GSVA" R package in R language;
immune-related score construction:
using immune cell infiltration scoring Gene set (PMID: 30837276), immport database [ ]https:// www.immport.org/) Calculating immune cell and immune channel activity scores of patients by means of ssGSEA method in GSVA R package;
performing pairwise correlation analysis of the metabolite scores with the above scores, selecting entries of significant correlation (P < 0.05), calculating immune correlation scores (defined as the sum of absolute values of Pearson correlation coefficients each having significant correlation) for each metabolite;
metabolic antagonistic molecule pair screening:
using the "survivinal" R package in R language, single factor COX regression analysis was performed on OS using metabolite scores to screen for metabolites with significant Prognostic significance and define a Prognostic Index (PI); statistically analyzing the metabolite score difference in the responsive/non-responsive groups in the gastric cancer immunotherapy cohort, and calculating a predictive index (Therapeutic Index, TI) of the metabolite according to the level of the score in the two groups;
screening metabolic pairs of which two corresponding metabolites have different TI or PI in metabolic reactions, wherein the metabolic pairs are defined as metabolic antagonistic molecule pairs and corresponding metabolic antagonistic reactions;
clinical cohort validation of metabolic antagonistic molecule pairs:
the antagonistic pair nicotinamide- & gt N-methyl nicotinamide with the highest immune score is selected, serum samples of stomach cancer patients receiving immunotherapy in southern hospitals of southern medical universities are collected, the serum concentrations of metabolites nicotinamide and N-methyl nicotinamide are respectively measured by ELISA detection kits, and the relationship between the nicotinamide/N-methyl nicotinamide ratio and the therapeutic effect of the immunotherapy is analyzed.
The measurement was performed using a sandwich enzyme-linked immunosorbent assay (ELISA) with a commercial monoclonal antibody (mAb) against nicotinamide or N-methylnicotinamide as the capture antibody and a rabbit polyclonal antibody No. 3 (RT 3-IgG) as the detection antibody.
And (3) collecting peripheral blood of a patient by using an EDTA anticoagulant tube, wherein the blood collection amount is not less than 2mL, and immediately and uniformly mixing the peripheral blood and the blood after blood collection. Centrifuging blood collection tube at 4deg.C for 10min at 1600g, packaging upper layer blood plasma into enzyme-removed EP tube, centrifuging (4deg.C, 160 g,10 min) for a second time to obtain supernatant, i.e. blood plasma sample, and performing subsequent experiment or preserving at-80deg.C.
To quantitatively detect nicotinamide and N-methylnicotinamide concentrations in plasma, measurement is performed using a sandwich enzyme-linked immunosorbent assay (ELISA). Human nicotinamide ELISA kit (Cat#2H-KMLJh 312339), human N-methylnicotinamide ELISA kit (Cat#2H-KMLJh 315351) was from CAMILO BIOLOGICAL. Plasma samples were diluted in sample buffer (50 mM Tris-HCl,100mM NaCl, 0.2% Triton X-100 and 0.2% BSA, pH 7.6) and incubated at 37℃for 90min. After washing the plates, they were incubated with pAb RT3-IgG for 90min at 37℃and then with goat anti-rabbit IgG for 60min at 37 ℃. The plate was then rinsed again and TMB/H2O2 was added as a peroxidase substrate to initiate the peroxidase reaction. After 20min at room temperature, the reaction was stopped by adding 0.5M H2SO 4. Optical density was measured with a microplate reader (Siemens, USA) at 462 nm. Nicotinamide and methylnicotinamide concentration units are nanograms per milligram (ng/mg).
Example 1: implementation flow of the invention
1. In the study, firstly, a gene expression matrix and clinical pathology information of a patient are downloaded from two groups of gene chip transcriptome data (GSE 62254/PRJEB 25780), and 299 transcriptome expression data, clinical information such as age, sex, diagnosis, pathology type, diagnosis date, total survival time, survival state and the like, and 45 transcriptome data and optimal objective response information of anti-PD-1 treatment are finally obtained. The metabolic reactions of all compounds were collected from the KEGG database and sorted into "a-B" form of metabolic molecule pairs according to the chemical reaction equation (e.g., four molecule pairs of chemical equation a+c→b+d, which may be sorted into a-B, A-D, C-B, C-D).
2. Subsequently, based on metabolite-protein interaction information published by Chen et al (PMID: 34247449), collecting protein molecules of each metabolite interaction, converting the proteins into corresponding encoding genes as a gene set for the metabolite scores (1807 total metabolites), and calculating the activity scores of the respective metabolites of the transcriptome sample by using ssGSEA algorithm in the "GSVA" R package from the metabolite gene set; meanwhile, the immune cell and immune channel activity scores of the patient are calculated by using 25 immune cell infiltration scoring gene sets (which are arranged from PMID (R): 30837276) and 17 immune response related channel gene sets in an Immport database and using the ssGSEA algorithm in a GSVA R package, so that the immune cell and immune channel activity scores of each sample respectively have 25+17 items.
3. In the GSE62254 gastric cancer dataset, a single factor COX regression analysis was performed on total survival (OS) based on the metabolite scores calculated in example two using the "survivinal" R package, screening for metabolites with significant Prognostic significance and defining a Prognostic Index (PI) for a total of 142 metabolites. Wherein, if metabolite HR >1 and P <0.05, pi=0; if metabolite HR <1 and P <0.05, pi=1; and metabolic molecule pairs with opposite PI were selected therefrom, 41 pairs in total.
On the other hand, in the gastric cancer immunotherapy queue PRJEB25780, the difference of metabolite scores in the response/non-response group (n=12:33) is analyzed by using t-test statistics, and metabolic molecule pairs with absolute values of the a-B static statistics being larger than 1 and positive and negative to each other are selected, 42 pairs are total, and the prediction index (Therapeutic Index, TI) of each metabolite is used for calculating the static statistics of the P value, and the larger the absolute value is, the more remarkable the difference is; TI is positive, i.e., the response group is greater than the non-response group, and if TI is negative, the non-response group is greater than the response group.
Finally, the screened metabolic molecule pairs are integrated and de-duplicated, and finally 78 pairs of metabolic antagonistic molecules and corresponding metabolic antagonistic reactions are obtained for immune correlation evaluation.
4. In the 78 pairs of metabolic antagonistic molecules screened in the third example, based on the immune cell and immune channel activity scores calculated in the previous step, a pairwise correlation analysis was performed on the metabolites and the immune scores in 299 samples of the GSE62254 gene chip, 42 correlation entries with 25 immune cells and 17 immune channels were obtained in total for each metabolite, entries with significant correlations were selected, and the immune correlation score (Immune Correlation Score) of each metabolite was calculated and defined as the sum of the absolute values of Pearson correlation coefficients with significant correlations. Of these, nicotinamide- > N-methylnicotinamide (KEGG REACTION: R01269) has the highest immune-related score in the 78 pairs of metabolic antagonistic molecules (FIG. 2), and has a significant difference in correlation with multiple immune cells (FIGS. 3-4).
Example 2: clinical cohort validation of nicotinamide metabolism antagonistic molecule pairs
1. Fresh whole blood samples from gastric cancer patients receiving immunotherapy from 10 months 2020 to 3 months 2022 in southern hospitals of southern medical university were collected, blood cells were removed by centrifugation, serum samples were obtained, and the concentrations of metabolites nicotinamide and N-methylnicotinamide were measured respectively using ELISA detection kits.
Case selection criteria were: the patient is diagnosed with gastric cancer through histopathology, and PD-1/PD-L1 immune checkpoint inhibitor is used in the treatment process; complete treatment records are available during treatment and at least 1 treatment effect evaluation is obtained after receiving immunotherapy. A total of 64 serum samples of 38 patients were finally obtained, of which 26 serum was collected at the baseline state of treatment and 38 serum was collected after immunotherapy; of 38 gastric cancer patients, 11 patients were evaluated for Partial Response (PR), 20 were disease progression (Progressive disease, PD), and 7 were Stable (SD).
Cases with efficacy evaluation of PR are divided into treatment response groups, cases with efficacy evaluation of PD and SD are divided into treatment non-response groups, the differences between groups of the treatment baseline and the ratio of nicotinamide to N-methylnicotinamide after treatment are counted by Prism 8.0 software, t-test statistics are adopted by using independent samples, paired t-test statistics are adopted between the same patient treatment baseline and the samples after treatment, and a P value of less than 0.05 is considered to have statistical significance.
The results showed that the ratio of peripheral blood (PR, n=16) of the patients in the treatment-responsive group was significantly higher than that of the peripheral blood (SD/PD, n=62) in the non-responsive group (fig. 5A); in peripheral blood samples of the same patient before and after receiving immunotherapy, the nicotinamide/N-methylnicotinamide ratio was significantly increased (p=0.0003) compared to baseline for all treatment-responsive patients, while the ratio was decreased (p=0.0002) for the majority of non-responsive patient samples (fig. 5B-5C).
2. Study of the trend of the ratio of peripheral blood nicotinamide to N-methylnicotinamide of 3 typical gastric cancer patients at different treatment nodes, and measurement of metabolite content after collecting peripheral blood and separating serum is also shown in FIG. 6; patent A-C represents 3 patients; the abscissa indicates the time of blood sample collection, PD indicates disease progression (treatment non-response), PR disease remission (treatment response), and Pre-ICIs are prior to receiving immunotherapy. When the efficacy is evaluated as PR, the ratio is increased; the ratio decreases as the disease Progresses (PD). Imaging of 3 patients at the time point of serum collection was also obtained, and the results are shown in fig. 7, with red arrows showing the location of the lesions after treatment. 5-FU, 5-fluorouracil; TP, albumin paclitaxel + cisplatin; IRI, i Li Tikang; PTX, paclitaxel liposome.
The present invention has been described in detail in the above embodiments, but the present invention is not limited to the above examples, and various changes can be made within the knowledge of those skilled in the art without departing from the spirit of the present invention. Furthermore, embodiments of the invention and features of the embodiments may be combined with each other without conflict.
Claims (10)
1. A marker for predicting the efficacy of an immunotherapy and/or chemotherapy of a tumor, comprising nicotinamide and N-methylnicotinamide.
2. The marker of claim 1, wherein the immunotherapy comprises treatment with an immune checkpoint inhibitor; preferably, the immune checkpoint inhibitor includes, but is not limited to, at least one of a PD-1 antibody, a PD-L1 antibody, CTLA-4.
3. The marker of claim 1, wherein the chemotherapeutic agent comprises at least one of 5-fluorouracil, a taxoid, a platinum group, and i Li Tikang.
4. A marker according to any one of claims 1 to 3, wherein said neoplasm comprises benign neoplasm and malignant neoplasm, including, but not limited to, at least one of intestinal cancer, lung cancer, melanoma, gastric cancer, squamous cell carcinoma, fibroma, pancreatic cancer, lipoma, vascular endothelial tumor, osteosarcoma, glomeruloma, osteoma, giant cell tumor, meningioma, lymphoma, thyroid cancer, liver cancer, ovarian cancer, head and neck cancer, breast cancer, cervical cancer, renal cancer, bladder cancer, prostate cancer, esophageal cancer, ovarian cancer and cholangiocarcinoma; preferably, the tumor is gastric cancer.
5. A detection reagent comprising a reagent for quantitatively detecting the contents of nicotinamide and N-methylnicotinamide according to any one of claims 1 to 4; preferably, the detection reagent comprises a reagent for detecting nicotinamide and N-methylnicotinamide content by at least one of an enzyme-linked immunosorbent assay, western blot, radioimmunoassay, immunohistochemical staining kit, immunoprecipitation assay kit, complement fixation assay, microarray and protein chip; preferably, the detection reagent comprises an antibody.
6. Use of a marker according to any one of claims 1 to 4 or a detection reagent according to claim 5 for the manufacture of a product for predicting the efficacy of a tumour immunotherapy and/or chemotherapy.
7. A product comprising the detection reagent of claim 5.
8. The product of claim 7, wherein the method of using the product comprises:
s1: detecting the content of nicotinamide and N-methylnicotinamide in a sample to be detected;
s2: calculating the ratio of nicotinamide to N-methylnicotinamide according to the content of nicotinamide and N-methylnicotinamide, and predicting the curative effect of immunotherapy and/or chemotherapy according to the ratio of nicotinamide to N-methylnicotinamide;
if the ratio of nicotinamide to N-methylnicotinamide is significantly higher than before treatment, immunotherapy and/or chemotherapy is effective for the treatment of the subject; if the ratio of nicotinamide to N-methylnicotinamide is significantly lower than before treatment, the immunotherapy and/or chemotherapy has no or insignificant therapeutic effect on the subject.
9. A detection system, comprising:
a detection device for determining the nicotinamide and N-methylnicotinamide content in a sample of a subject;
the analysis device is used for obtaining the detection result, calculating the ratio of nicotinamide to N-methylnicotinamide, and predicting the curative effect of immunotherapy and/or chemotherapy according to the ratio of nicotinamide to N-methylnicotinamide;
if the ratio of nicotinamide to N-methylnicotinamide is significantly higher than before treatment, immunotherapy and/or chemotherapy is effective for the treatment of the subject; if the ratio of nicotinamide to N-methylnicotinamide is significantly lower than before treatment, the immunotherapy and/or chemotherapy has no or insignificant therapeutic effect on the subject.
10. A computer readable storage medium storing a computer program which, when executed by a processor, performs the functions of the detection system of claim 9.
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