Use of 5-oxoproline in the preparation of a product for diagnosing chemotherapy-induced cardiomyopathy

Abstract

The application discloses that 5-oxoproline can be used as a biomarker for diagnosing chemotherapy-induced cardiomyopathy, and for the first time provides a blood metabolic marker for assisting in predicting and early diagnosing chemotherapy drug-induced cardiomyopathy, which has high accuracy and diagnostic reference value. By accurately determining the content of the small molecule metabolic marker 5-oxoproline in blood, the diagnosis of early myocardial injury induced by chemotherapy drugs will no longer completely rely on conventional non-specific myocardial injury markers and imaging methods, but will rely on the content change of metabolic products in the blood of patients as an objective index, thus advancing the time window for discovering subclinical myocardial injury, significantly improving the early diagnosis detection rate, simplifying the diagnosis process, providing an opportunity for early intervention, helping to prevent or reverse the further aggravation of chemotherapy-induced cardiomyopathy, and thus improving the overall survival prognosis of tumor patients.

Description

Technical Field

[0001] This invention relates to novel applications of 5-oxoproline as a biomarker, particularly its application in the preparation of early diagnostic methods for chemotherapy-induced cardiomyopathy in cancer patients. Background Technology

[0002] According to the 2020 global cancer burden data released by the International Agency for Research on Cancer (IARC) of the World Health Organization, breast cancer has surpassed lung cancer to become the leading cause of cancer death worldwide, and it is also the most common malignant tumor among women. While various types of chemotherapy drugs (such as anthracyclines and novel HER2-targeted therapies) offer survival benefits, they also present various adverse drug reactions, particularly cardiotoxicity caused by chemotherapy, which may even outweigh the benefits of cancer treatment. Anthracyclines, the most classic chemotherapy drugs for cancer treatment, are widely used clinically due to their potent therapeutic effects. However, their clinical application is largely affected by cumulative and dose-dependent cardiotoxicity, which can ultimately lead to irreversible structural changes in the myocardium and progressive heart failure. Autopsy studies have shown that cardiotoxicity progresses from myocardial vacuolar degeneration to irreversible myocardial collagen accumulation. Therefore, anthracyclines, the most classic chemotherapy drugs for breast cancer treatment, can cause different types and degrees of cardiotoxicity, including myocardial contractile dysfunction and arrhythmias. One-third of cancer patients die from cardiovascular disease rather than the cancer itself, making it the leading cause of non-cancer-related death among cancer patients. Cardiovascular complications have become the most common cause of death among breast cancer patients. Therefore, early detection of cardiotoxicity from chemotherapy in breast cancer is crucial, as it provides an opportunity for early intervention, helps prevent or reverse further myocardial damage, and thus improves the overall survival prognosis of breast cancer.

[0003] Currently, clinical assessments of myocardial injury after chemotherapy include conventional echocardiography and biomarkers such as BNP and cTnI. Conventional echocardiography lacks sensitivity in detecting early subclinical cardiac injury, while changes in biomarkers such as BNP and cTnI often indicate significant myocardial damage, rather than an early stage of myocardial injury caused by breast cancer chemotherapy. Metabolomics, at the end of the gene, transcriptome, and proteome pathways, reflects ongoing biological changes. Unlike genomics and proteomics, which reflect in vivo differences, metabolomics extends its research scope to the interactions and effects between the body and its environment. Small molecule metabolites are not only the material basis for the body's life activities and biochemical metabolism but also reflect changes in the internal metabolic environment caused by certain external factors. Therefore, differences in the concentration of certain unique metabolites among individuals reflect both the intrinsic manifestations and extrinsic causes of disease. Thus, metabolomics analysis based on biological samples (such as serum, urine, and saliva) is helpful for the screening and early diagnosis of complex diseases.

[0004] Currently, there is a lack of simple and effective serum biomarkers for early diagnosis of myocardial injury after chemotherapy. Therefore, the search for specific, sensitive, economical, and non-invasive serum metabolic markers for the early diagnosis of myocardial injury after chemotherapy has significant clinical application value. Summary of the Invention

[0005] The purpose of this invention is to provide the application of 5-oxoproline as a biomarker in the preparation of products for diagnosing chemotherapy-induced cardiomyopathy. This invention also provides a product for diagnosing chemotherapy-induced cardiomyopathy in cancer patients.

[0006] To achieve the objectives of this invention, in one aspect, this invention provides the application of 5-oxyproline as a biomarker in the preparation of products for diagnosing chemotherapy-induced cardiomyopathy.

[0007] Addressing the challenge of early diagnosis of chemotherapy-induced cardiomyopathy in cancer patients, the inventors of this application employed LC-MS / MS to determine the levels of major metabolites in the blood. Specifically, the method involved further enrichment analysis of metabolites showing significant differences between two groups, screening for metabolites potentially involved in early myocardial injury, and further validation. Ultimately, 5-O-proline was determined to serve as a biomarker for the early diagnosis of chemotherapy-induced cardiomyopathy in cancer patients. This biomarker can complement current clinical assessments of post-chemotherapy myocardial injury in the early diagnosis of chemotherapy-induced cardiomyopathy in cancer patients, offering high accuracy and reducing reliance on conventional non-specific myocardial injury markers and imaging techniques. This significantly improves the early detection rate and simplifies the diagnostic process.

[0008] This invention addresses the shortcomings of existing technologies in diagnosing chemotherapy-induced cardiomyopathy in cancer patients, such as nonspecificity, low sensitivity, and the fact that myocardial injury is generally detected at a late stage, thus failing to achieve early diagnosis of myocardial injury after chemotherapy. It provides a biomarker suitable for early diagnosis of myocardial injury after chemotherapy. This diagnostic marker has good sensitivity and specificity for myocardial injury after chemotherapy, especially early-stage myocardial injury, enabling early detection and intervention. This is of great significance for improving the prognosis of heart failure and reducing mortality in patients with chemotherapy-induced cardiomyopathy.

[0009] When 5-oxoproline is used as a biomarker in the preparation of products for diagnosing chemotherapy-induced cardiomyopathy, it is targeted at the diagnosis of chemotherapy-induced cardiomyopathy in cancer patients. The cancer patients are preferably, but not limited to, breast cancer patients. The chemotherapy drugs are generally anthracycline drugs, such as, but not limited to, doxorubicin.

[0010] When 5-oxoproline is used as a biomarker in the preparation of products for diagnosing chemotherapy-induced cardiomyopathy, the products prepared include, but are not limited to, kits.

[0011] Currently, most methods in this field use imaging or conventional myocardial injury markers to diagnose myocardial injury. This invention is the first to propose using serum metabolomics technology to screen for biomarkers of myocardial injury after chemotherapy, and has discovered markers that are particularly suitable for the early diagnosis of myocardial injury after chemotherapy, providing a good diagnostic method for early myocardial injury that is difficult to detect.

[0012] On the other hand, the present invention also provides the application of reagents for detecting 5-oxoproline in the preparation of products for diagnosing chemotherapy-induced cardiomyopathy.

[0013] This invention has discovered that 5-oxoproline can serve as a diagnostic biomarker for chemotherapy-induced cardiomyopathy in cancer patients, particularly for the early diagnosis of this condition. Therefore, reagents for detecting 5-oxoproline can be used to prepare products for diagnosing chemotherapy-induced cardiomyopathy. These products, containing reagents for detecting 5-oxoproline, allow for the rapid determination of 5-oxoproline levels in the blood of patients to be diagnosed. The measured 5-oxoproline levels can then be used to diagnose cardiomyopathy in these patients.

[0014] When a product for diagnosing chemotherapy-induced cardiomyopathy is prepared using reagents that detect 5-oxoproline, the diagnostic target is cancer patients, especially breast cancer patients. The cardiomyopathy refers to cardiomyopathy induced by chemotherapy in cancer patients, and the chemotherapy typically uses anthracyclines, such as, but not limited to, doxorubicin.

[0015] A product for diagnosing chemotherapy-induced cardiomyopathy is prepared using a reagent for detecting 5-oxoproline. The product can be any type of product that can be used to diagnose chemotherapy-induced cardiomyopathy, such as, but not limited to, a kit for diagnosing chemotherapy-induced cardiomyopathy.

[0016] Finally, the present invention also provides a product for diagnosing chemotherapy-induced cardiomyopathy, the product containing a reagent for detecting 5-oxoproline.

[0017] The inventors of this application discovered that 5-oxoproline can serve as a biomarker for chemotherapy-induced cardiomyopathy. Using reagents for detecting 5-oxoproline, a product for diagnosing chemotherapy-induced cardiomyopathy was prepared, such as a reagent kit. This invention, by using reagents for detecting 5-oxoproline to prepare a product for diagnosing chemotherapy-induced cardiomyopathy, demonstrates diagnostic efficacy for chemotherapy-induced cardiomyopathy in cancer patients, particularly for the early diagnosis of this condition. By objectively examining changes in the 5-oxoproline content in the blood of cancer patients, the time window for detecting subclinical myocardial injury is advanced, significantly improving the early detection rate of chemotherapy-induced cardiomyopathy in cancer patients.

[0018] The product of this invention is used to diagnose chemotherapy-induced cardiomyopathy in cancer patients, including but not limited to breast cancer patients, and the chemotherapy drugs used include but are not limited to anthracyclines, such as doxorubicin.

[0019] This invention is the first to discover that 5-oxoproline can serve as a biomarker for diagnosing chemotherapy-induced cardiomyopathy. It also provides, for the first time, a blood metabolic marker for the auxiliary prediction and early diagnosis of chemotherapy-induced cardiomyopathy, exhibiting high accuracy and diagnostic value. By accurately measuring the content of the small-molecule metabolic marker 5-oxoproline in the blood, the diagnosis of early myocardial injury induced by chemotherapy no longer relies entirely on conventional non-specific myocardial injury markers and imaging techniques. Instead, it uses objective indicators such as changes in the content of metabolites in the patient's blood to advance the detection window of subclinical myocardial injury, significantly improving the early detection rate, simplifying the diagnostic process, providing opportunities for early intervention, and helping to prevent or reverse the further aggravation of chemotherapy-induced cardiomyopathy, thereby improving the overall survival prognosis of cancer patients. Attached Figure Description

[0020] Figure 1 This is a flowchart of the data analysis process for screening metabolic markers in this invention.

[0021] Figure 2 A classification chart showing the chemical classification of the metabolites obtained from screening.

[0022] Figure 3 A graph showing the fold change in metabolic differences due to significant differences in positive ion mode.

[0023] Figure 4 A graph showing the fold change in metabolic differences due to significant differences in negative ion patterns.

[0024] Figure 5 The pathway was enriched by combining differentially differentiated metabolites and differentially differentiated genes in mouse myocardial tissue.

[0025] Figure 6 Figure showing the changes in 5-oxoproline in mouse serum and myocardial tissue and its correlation with early decline in cardiac function.

[0026] Figure 7 A graph showing the sensitivity and specificity of 5-oxoproline and cTNT in mouse serum for diagnosing early myocardial injury.

[0027] Figure 8 A comparative graph showing the changes in serum 5-oxoproline, cTNI, and BNP in breast cancer patients during the early stages of doxorubicin chemotherapy.

[0028] Figure 9A graph showing the significant changes in LVEDD and IVST in breast cancer patients after doxorubicin chemotherapy and their correlation with the early decrease in 5-oxoproline. Detailed Implementation

[0029] To better illustrate the purpose, technical solution, and advantages of the present invention, the present invention will be further described below in conjunction with the accompanying drawings and specific embodiments.

[0030] Example 1

[0031] Screening of early blood metabolic markers for anthracycline-induced cardiomyopathy

[0032] 1. Laboratory animals and grouping

[0033] Sixteen C57 mice aged 6-8 weeks were randomly divided into an experimental group and a control group, with eight mice in each group.

[0034] The experimental group of mice underwent tumor-induced cardiac modeling (doxorubicin, 5 mg / kg, once), and cardiac function was assessed by echocardiography one week later.

[0035] 2. Extraction of metabolites from blood

[0036] (1) After tumor-induced heart disease modeling, the experimental group mice and the control group mice were anesthetized, the heart was removed, the heart was washed with pre-cooled 4°C physiological saline, the residual blood was drained, and a portion of the apex of the heart was quickly frozen in liquid nitrogen for myocardial tissue metabolomics analysis.

[0037] (2) After the myocardial tissue frozen in liquid nitrogen was slowly thawed at 4°C, an appropriate amount of sample was added to a pre-cooled methanol / acetonitrile / water solution (2:2:1, v / v), vortexed, sonicated at low temperature for 30 min, allowed to stand at -20°C for 10 min, centrifuged at 14000g at 4°C for 20 min, the supernatant was taken and vacuum dried, and 100 μL of acetonitrile water solution (acetonitrile:water = 1:1, v / v) was added to redissolve the sample for mass spectrometry analysis, vortexed, centrifuged at 14000g at 4°C for 15 min, and the supernatant was taken to obtain the metabolic extract.

[0038] 3. Targeted metabolomics analysis based on LC-MS / MS

[0039] Metabolites in the sample (metabolic extract) were separated by hydrophilic interaction chromatography. The sample was separated using a Vanquish LC ultra-high performance liquid chromatography (UHPLC) system with a HILIC column; column temperature 25℃; flow rate 0.3 mL / min; injection volume 2 μL; mobile phase composition A: water + 25 mM ammonium acetate + 25 mM ammonia; B: acetonitrile. The gradient elution program was as follows: 0-1.5 min, 98% B; 1.5-12 min, B linearly decreased from 98% to 2%; 12-14 min, B maintained at 2%; 14-14.1 min, B linearly decreased from 2% to 98%; 14.1-17 min, B maintained at 98%. Throughout the analysis, the sample was placed in an autosampler at 4℃.

[0040] After separation using a Vanquish LC ultra-high performance liquid chromatography (UHPLC) system, samples were analyzed by mass spectrometry using a Q-Exactive series mass spectrometer (Thermo). Electrospray ionization (ESI) was employed in both positive and negative ion modes. The ESI source and mass spectrometry settings were as follows: Auxiliary heating gas 1 (Gas1): 60, Auxiliary heating gas 2 (Gas2): 60, Curtain gas (CUR): 30 psi, Ion source temperature: 600℃, Spray voltage (ISVF) ±5500V (both positive and negative modes); Primary mass-to-charge ratio detection range: 80-1200 Da, resolution: 60000, cumulative scan time: 100 ms; Secondary mass-to-charge ratio was acquired using a segmented acquisition method, with a scan range of 70-1200 Da, secondary resolution: 30000, cumulative scan time: 50 ms, and dynamic exclusion time: 4 s.

[0041] 4. Analyze and validate the screened potential metabolic markers.

[0042] The raw data were converted to .mzXML format using ProteoWizard, and then peak alignment, retention time correction, and peak area extraction were performed using XCMS software. The data extracted by XCMS were first subjected to metabolite structure identification and data preprocessing, followed by experimental data quality assessment, and finally data analysis.

[0043] The data analysis includes univariate statistical analysis, multidimensional statistical analysis, screening of differentially expressed metabolites, correlation analysis of differentially expressed metabolites, and KEGG pathway analysis. The specific workflow is shown in the attached document. Figure 1 As shown.

[0044] In this embodiment, 1106 metabolites were identified after the positive and negative ion modes were combined. The number of metabolites identified by the positive and negative ion modes is shown in Table 1.

[0045] Table 1. Statistics on the number of metabolites identified by positive and negative ion modes.

[0046] Detection mode Number of metabolites identified Positive ion mode (Pos) 628 Negative ion mode (Neg) 478

[0047] All metabolites (including those identified by both positive and negative ions) were classified and statistically analyzed according to their chemical taxonomy. The percentage of each type of metabolite is shown in the attached figure. Figure 2 As shown.

[0048] Differential metabolites were screened through univariate and multidimensional statistical analyses. The variable importance for the projection (VIP) values ​​obtained from the OPLS-DA model can be used to measure the influence and explanatory power of each metabolite's expression pattern on the classification of each group of samples, thus identifying biologically significant differentially expressed metabolite molecules. Metabolites with a VIP > 1 are generally considered to have made a significant contribution to the model's explanation.

[0049] Metabolomics typically uses strict screening criteria of OPLS-DA VIP>1 and P value<0.05 for significantly differentially expressed metabolites, and this experiment adopted these criteria. The fold change of the identified significantly differentially expressed metabolites is visually represented by a bar chart, as shown in the attached figure. Figure 3 and attached Figure 4 As shown.

[0050] Appendix Figure 3 and 4 In the graph, the horizontal axis represents the log2 FC value of the differentially regulated metabolite, which is the logarithm of the differential metabolite's fold change to base 2. The vertical axis represents the significantly differentially regulated metabolites. Red indicates upregulation of the differentially regulated metabolite, and green indicates downregulation of the differentially regulated metabolite.

[0051] Metabolomics revealed 79 differentially expressed metabolites after doxorubicin-induced early myocardial injury. Combined analysis of transcriptomics (differentially expressed genes, Benjamini-Hochberg corrected P < 0.05 and |log2[foldchange]| ≥ 1) and metabolomics (differentially expressed metabolites, orthogonal partial least squares discriminant analysis, VIP > 2) was performed using the MetaboAnalyst online tool (https: / / www.metaboanalyst.ca). The results are attached. Figure 5 As shown.

[0052] From the appendix Figure 5 It can be seen that differentially metabolites and differentially expressed genes are both enriched in the glutathione metabolic pathway. Among them, the metabolite with significant changes in the glutathione metabolic pathway is 5-oxoproline.

[0053] The detection methods for the screened metabolites that can serve as potential biomarkers are as follows:

[0054] (1) Sample pretreatment

[0055] Synthesis of 5-Oproline internal standard: 1 mg / mL glutamate-d5 solution was prepared with 0.1 N hydrochloric acid, and 5-Oproline-d5 internal standard solution was synthesized by heating at 80 °C for 15 hours. The pH was adjusted back to neutral with ammonia water to obtain 5-Oproline internal standard.

[0056] Preparation of internal standard working solution: Dilute the 5-oxoproline internal standard 200 times with a 75% acetonitrile aqueous solution containing 0.2% formic acid to prepare the 5-oxoproline internal standard working solution;

[0057] Sample preparation: Take 50 μL of standard curve, quality control sample and test sample respectively and add them to 1.5 mL centrifuge tubes. Add 400 μL of internal standard working solution, vortex for 60 seconds, centrifuge at 13000 rpm for 4 degrees for 10 minutes, and transfer 200 μL of supernatant to 2.2 mL 96-well plate for testing.

[0058] (2) Liquid phase method

[0059] Metabolites in the sample were separated using a Phenomenex Kinetex F5 column (2.6 μm, 2.1 × 100 mm) under the following chromatographic conditions:

[0060] Mobile phase A is 0.1% formic acid in water;

[0061] Mobile phase B is 0.1% formic acid acetonitrile;

[0062] The flow rate was 0.25 ml / min;

[0063] The column temperature is 25℃;

[0064] The gradient elution conditions are shown in Table 2 below.

[0065] Table 2 Gradient elution conditions

[0066] Time (min) A(％) B(％) 0 99 1 1.2 99 1 2 1 99 3 1 99 3.01 99 1 4 99 1

[0067] (3) Mass spectrometry

[0068] AB SCIEX Triple Quad TM The 4500MD liquid chromatography-tandem mass spectrometry system employed ESI+ and multiple reaction monitoring (MRM) modes for mass spectrometry scanning. The curtain gas (CUR) setting was 35 psi; the collision gas (CAD) setting was 9 psi; the voltage was +5500 V; the desolvation gas temperature was 500 °C; the heating gas (GS1) setting was 50 psi; and the auxiliary gas (GS2) setting was 50 psi. The mass spectrometry channel parameters are shown in Table 3 below.

[0069] Table 3 Mass Spectrometry Channel Parameters

[0070] Analyte Q1 Q3 Dwell Time (msec) DP EP CE CXP P-Glu 130.1 84.0 100 60 10 18 9 P-Glu-d5 135.2 89.2 50 60 10 20 9

[0071] (4) Calibrators and quality control products

[0072] The 5-oxyproline standard was prepared into a 50mM primary stock solution with water, diluted with water to a 4mM secondary stock solution, and then diluted and mixed with water to obtain standard curves and quality control products of different concentrations, as shown in Table 4 below.

[0073] Table 4 Standard curves and quality control materials at different concentrations

[0074]

[0075] The content of 5-oxoproline was further detected in the serum and myocardial tissue of mice with doxorubicin-induced early myocardial injury using a developed targeted LC / MS method. The results are shown in the attached figure. Figure 6 As shown.

[0076] From the appendix Figure 6 It can be seen that 5-oxoproline levels decreased significantly and were negatively correlated with global longitudinal strain (GLS), an indicator of early cardiac function decline.

[0077] Meanwhile, ROC analysis was performed based on a GLS decrease of more than 15% as a diagnostic criterion for early myocardial injury. The results are shown in the attached figure. Figure 7 As shown.

[0078] From the appendix Figure 7 It is known that 5-Oproline has high diagnostic sensitivity and specificity and can be used as a biomarker for chemotherapy-induced cardiomyopathy in cancer patients.

[0079] Example 2

[0080] Validation of 5-Oproline as a biomarker in the early diagnosis of chemotherapy-induced cardiomyopathy

[0081] This embodiment is based on the Good Clinical Practice (GCP) guidelines for drug clinical trials, using a protocol approved by the ethics committee, and has been reviewed and approved by the ethics committee.

[0082] This study focuses on female patients aged 18 to 70 years with pathologically confirmed breast cancer who have no heart discomfort symptoms, no history of structural heart disease, and have not previously used anthracycline drugs for treatment.

[0083] Sample Size Calculation: Based on previous CMR studies, extracellular matrix volume (ECV) is one of the most valuable and sensitive indicators reflecting changes in the myocardium. In our preliminary study, which included 10 patients (early myocardial injury) and 10 controls, the mean ECVs were 30% and 24%, respectively. The standard deviation of ECV across the entire group was 0.3. The difference between the chemotherapy and control groups in the preliminary study was 4%. Based on the sample ratio (n CMP / n Control = 1), a type I error (both sides) of 5%, and a power of 0.8, a minimum sample size of 42 subjects per group was expected. In this project, each subject underwent three sample collections (baseline, initial follow-up, and final follow-up). The baseline and initial follow-up were analogous to the control and chemotherapy groups in the preliminary study; therefore, a final sample size of at least 42 subjects was expected. Considering the possibility of loss to follow-up and dropouts during follow-up, this embodiment used a sample size of 60 subjects.

[0084] Experimental Methods: Participants were enrolled and followed up according to the research protocol requested in the ethical application. Blood samples were collected from subjects at baseline (before chemotherapy), at the end of the first cycle of anthracycline therapy (during the second dose), and after the completion of all anthracycline therapy cycles. Serum samples were collected and stored for subsequent metabolite detection and cTNI and BNP testing. Cardiac function was assessed by echocardiography at baseline and after chemotherapy, and data were collected and analyzed. Specific data collection methods were as follows:

[0085] Subject serological baseline collection: Serological data were collected from subjects who met the inclusion and exclusion criteria before the start of doxorubicin treatment as baseline indicators.

[0086] Initial follow-up serological collection: 4-5 ml of blood was collected from the subject at the end of the first course of doxorubicin treatment (during the second administration) as the initial follow-up sample;

[0087] Serological collection at the last follow-up: 4-5 ml of blood was collected from the subject after the completion of the entire course of doxorubicin treatment as the final follow-up sample.

[0088] After all blood samples were collected, serum samples were collected by centrifugation for metabolite detection, as well as cTNI and BNP testing. The test results are attached. Figure 8 As shown.

[0089] Appendix Figure 8 The image shows the changes in serum 5-oxoproline, cTNI, and BNP in breast cancer patients during the early stages of doxorubicin chemotherapy in this embodiment. Figure 8 It can be seen that, compared with cTNI and BNP (conventional markers of myocardial injury), 5-oxoproline shows more significant changes in the early stages of myocardial injury in oncological heart disease.

[0090] Cardiac function was assessed by echocardiography at baseline and after chemotherapy, and data were collected and analyzed. The results are attached. Figure 9 As shown.

[0091] From the appendix Figure 9 It can be seen that after doxorubicin chemotherapy, the left ventricular end-diastolic diameter (LVEDD) and interventricular septal thickness (IVST) of breast cancer patients changed significantly and were correlated with the early decrease in 5-oxoproline.

[0092] The experimental results above show that 5-oxoproline exhibits significant changes in the early stages of chemotherapy-induced cardiomyopathy in cancer patients, with a marked decrease in its content. This decrease is negatively correlated with global longitudinal strain (GLS), an indicator of early cardiac function decline. Furthermore, compared to cTNI and BNP (conventional myocardial injury markers), 5-oxoproline shows more pronounced changes in myocardial injury in cancer-related heart disease. Clinical trials further confirmed that significant changes in LVEDD and IVST after doxorubicin chemotherapy in breast cancer patients were correlated with a certain degree of early 5-oxoproline decrease. Therefore, 5-oxoproline can serve as a biomarker for the early diagnosis of chemotherapy-induced cardiomyopathy in cancer patients. Diagnosis can be made through objective indicators such as changes in 5-oxoproline levels in the patient's blood, overcoming the limitations of current technologies that rely entirely on conventional non-specific myocardial injury markers and imaging techniques for diagnosing chemotherapy-induced cardiomyopathy in cancer patients. This invention uses 5-oxyproline as a diagnostic marker for chemotherapy-induced cardiomyopathy. It can be combined with imaging and other methods, which not only has high accuracy and diagnostic reference value, but also effectively improves the early detection rate, providing an opportunity for early intervention. It helps to prevent or reverse the further aggravation of chemotherapy-induced myocardial damage, which has significant clinical significance.

[0093] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention and are not intended to limit the scope of protection of the present invention. Although the present invention has been described in detail with reference to preferred embodiments, those skilled in the art should understand that modifications or equivalent substitutions can be made to the technical solutions of the present invention without departing from the essence and scope of the technical solutions of the present invention.

Claims

The application of 1,5-Oproline as a biomarker in the preparation of products for diagnosing chemotherapy-induced cardiomyopathy, wherein the chemotherapy drug used is doxorubicin.

2. The application as described in claim 1, characterized in that, The concentration of 5-oxoproline decreased in chemotherapy-induced cardiomyopathy; And / or, the product is a kit.

3. Application of reagents for detecting 5-oxoproline in the preparation of products for diagnosing chemotherapy-induced cardiomyopathy, wherein the chemotherapy drug used is doxorubicin.

4. The application as described in claim 3, characterized in that, The concentration of 5-oxoproline decreased in chemotherapy-induced cardiomyopathy; And / or, the product is a kit.

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