Metabolic markers for distinguishing hypertrophic cardiomyopathy from left ventricular hypertrophy and uses thereof

Abstract

The application belongs to the technical field of molecular biology, and particularly relates to metabolic markers for distinguishing hypertrophic cardiomyopathy and left ventricular hypertrophy and application. The application analyzes the metabolome of hypertrophic cardiomyopathy (HCM) patients, left ventricular hypertrophy (LVH) patients caused by non-hypertrophic cardiomyopathy and healthy people, finds that carnitine C16:2, carnitine C14:0, carnitine C16:0, carnitine C18:0 and carnitine C18:1 are differentially expressed in HCM patients and LVH patients, pyridoxine phosphate, ito acid, adenosine monophosphate, adenosine diphosphate and adenosine triphosphate are differentially expressed in HCM patients and healthy people, lysine base, methyl glutamic acid, acetyl proline, malate semialdehyde and citramalate are differentially expressed in LVH patients and healthy people, and ROC curve analysis shows excellent prediction effect, strong specificity and high sensitivity.

Description

Technical Field

[0001] This invention belongs to the field of molecular biology technology, specifically relating to metabolic markers and their applications for differentiating hypertrophic cardiomyopathy from left ventricular hypertrophy. Background Technology

[0002] Left ventricular hypertrophy (LVH), also known as left ventricular enlargement, is caused by various factors such as hypertension and heart disease, leading to thickening of the left ventricular wall. This can result in a series of complications, including decreased cardiac function, myocardial infarction, and pulmonary hypertension. Once LVH develops, aggressive treatment is necessary. For example, hypertension and coronary heart disease require antihypertensive therapy, as well as treatment to improve myocardial blood flow. Additionally, anticoagulant and antiplatelet drugs, such as aspirin and clopidogrel, are needed to treat the underlying disease and allow the LVH to gradually return to normal levels.

[0003] Hypertrophic cardiomyopathy (HCM) is clinically characterized by left ventricular hypertrophy, pathologically manifested as enlarged and disordered cardiomyocytes, interstitial fibrosis, and inflammatory cell infiltration. Patients with HCM may develop complications including left ventricular outflow tract obstruction, arrhythmias, heart failure, and even sudden cardiac death, which is particularly prominent in adolescents. Therefore, it can impose a significant economic, social, and medical burden on the healthcare system. Currently, the screening and diagnosis of HCM mainly rely on imaging methods. However, numerous factors contribute to left ventricular hypertrophy, and imaging methods alone cannot differentiate between left ventricular hypertrophy caused by hypertrophic cardiomyopathy and that caused by non-hypertrophic cardiomyopathy. Therefore, screening for biomarkers that differentiate between left ventricular hypertrophy caused by hypertrophic cardiomyopathy and non-hypertrophic cardiomyopathy, and accurately diagnosing hypertrophic cardiomyopathy, is particularly important in this field. Summary of the Invention

[0004] The purpose of this invention is to accurately determine left ventricular hypertrophy caused by hypertrophic cardiomyopathy and non-hypertrophic cardiomyopathy, and to accurately distinguish between left ventricular hypertrophy caused by hypertrophic cardiomyopathy and non-hypertrophic cardiomyopathy.

[0005] This invention provides biomarkers for distinguishing between hypertrophic cardiomyopathy and left ventricular hypertrophy, including one or more of carnitine C16:2, carnitine C14:0, carnitine C16:0, carnitine C18:0, and carnitine C18:1;

[0006] The left ventricular hypertrophy mentioned refers to left ventricular hypertrophy caused by non-hypertrophic cardiomyopathy.

[0007] This invention also provides the application of the biomarkers described in the above technical solution in the preparation of products that differentiate between hypertrophic cardiomyopathy and left ventricular hypertrophy;

[0008] The left ventricular hypertrophy mentioned refers to left ventricular hypertrophy caused by non-hypertrophic cardiomyopathy.

[0009] The present invention also provides biomarkers associated with hypertrophic cardiomyopathy, including one or more of pyridoxine phosphate, itoric acid, adenosine monophosphate, adenosine diphosphate, and adenosine triphosphate.

[0010] The present invention also provides the application of the biomarkers described in the above technical solution in the preparation of products for diagnosing hypertrophic cardiomyopathy.

[0011] The present invention also provides biomarkers associated with left ventricular hypertrophy, including one or more of lysine, methylglutamic acid, acetylproline, malic semialdehyde and citric acid;

[0012] The left ventricular hypertrophy mentioned refers to left ventricular hypertrophy caused by non-hypertrophic cardiomyopathy.

[0013] The present invention also provides the application of the biomarkers described in the above technical solution in the preparation of products for diagnosing left ventricular hypertrophy; wherein the left ventricular hypertrophy is left ventricular hypertrophy caused by non-hypertrophic cardiomyopathy.

[0014] Preferably, the product includes a reagent kit.

[0015] The present invention also provides a kit for differentiating hypertrophic cardiomyopathy from left ventricular hypertrophy, the kit comprising reagents for detecting the levels of the biomarkers described in the above technical solutions;

[0016] The left ventricular hypertrophy mentioned refers to left ventricular hypertrophy caused by non-hypertrophic cardiomyopathy.

[0017] The present invention also provides a kit for diagnosing hypertrophic cardiomyopathy, the kit comprising reagents for detecting the levels of the biomarkers described in the above-described technical solutions.

[0018] The present invention also provides a kit for diagnosing left ventricular hypertrophy, the kit comprising reagents for detecting the levels of the biomarkers described in the above technical solutions;

[0019] The left ventricular hypertrophy mentioned refers to left ventricular hypertrophy caused by non-hypertrophic cardiomyopathy.

[0020] Beneficial effects:

[0021] This invention analyzes the metabolomes of patients with hypertrophic cardiomyopathy (HCM), patients with left ventricular hypertrophy (LVH) caused by non-hypertrophic cardiomyopathy, and healthy individuals. The results show that carnitine C16:2, carnitine C14:0, carnitine C16:0, carnitine C18:0, and carnitine C18:1 are differentially expressed in both HCM and LVH patients. ROC curve analysis demonstrates excellent predictive performance with high specificity and sensitivity. Furthermore, markers distinguishing between HCM and LVH, including pyridoxine phosphate, itoric acid, adenosine monophosphate, adenosine diphosphate, and adenosine triphosphate, are differentially expressed in both HCM and healthy individuals. ROC curve analysis also shows excellent predictive performance with high specificity and sensitivity. Finally, markers distinguishing between HCM and LVH, including lysine, methylglutamic acid, acetylproline, malate semialdehyde, and citrate, are differentially expressed in both LVH and healthy individuals. ROC curve analysis also shows excellent predictive performance with high specificity and sensitivity. Attached Figure Description

[0022] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the accompanying drawings used in the embodiments will be briefly described below.

[0023] Figure 1 To derive ROC curves for differentially metabolites between HCM and LVH in the cohort;

[0024] Figure 2 Box plots were used to derive differential metabolites between HCM and LVH in the cohort; where NS indicates no significant difference; * indicates significant difference, P < 0.05; ** indicates significant difference, P < 0.01; *** indicates significant difference, P < 0.001.

[0025] Figure 3 To derive ROC curves for differentially metabolites between the HCM and NC groups in the cohort;

[0026] Figure 4 Box plots were used to derive differential metabolites between the HCM and NC groups in the cohort; where NS indicates no significant difference; * indicates significant difference, P < 0.05; ** indicates significant difference, P < 0.01; *** indicates significant difference, P < 0.001.

[0027] Figure 5 To derive ROC curves for differential metabolites between the LVH and NC groups in the cohort;

[0028] Figure 6Box plots were used to derive differential metabolites between the LVH and NC groups in the cohort; where NS indicates no significant difference; * indicates significant difference, P < 0.05; ** indicates significant difference, P < 0.01; *** indicates significant difference, P < 0.001.

[0029] Figure 7 To verify the ROC curves of differential metabolites among the HCM, LVH, and NC groups in the cohort;

[0030] Figure 8 Box plots were used to validate differential metabolites among the HCM, LVH, and NC groups in the cohort; where NS indicates no significant difference; * indicates significant difference (P < 0.05); ** indicates significant difference (P < 0.01); *** indicates significant difference (P < 0.001). Detailed Implementation

[0031] This invention provides biomarkers for distinguishing between hypertrophic cardiomyopathy and left ventricular hypertrophy, including one or more of carnitine C16:2, carnitine C14:0, carnitine C16:0, carnitine C18:0 and carnitine C18:1; wherein the left ventricular hypertrophy is left ventricular hypertrophy caused by non-hypertrophic cardiomyopathy.

[0032] In one embodiment, the carnitine C16:2, carnitine C14:0, carnitine C16:0, carnitine C18:0, and carnitine C18:1 are carnitine C16:2, carnitine C14:0, carnitine C16:0, carnitine C18:0, and carnitine C18:1 in blood plasma, respectively.

[0033] In one embodiment, the biomarker may be a combination of two or more of carnitine C16:2, carnitine C14:0, carnitine C16:0, carnitine C18:0, and carnitine C18:1; in another embodiment, the biomarker may be a combination of three or more of carnitine C16:2, carnitine C14:0, carnitine C16:0, carnitine C18:0, and carnitine C18:1; in yet another embodiment, the biomarker may be a combination of four or more of carnitine C16:2, carnitine C14:0, carnitine C16:0, carnitine C18:0, and carnitine C18:1; in yet another embodiment, the biomarker may be a combination of carnitine C16:2, carnitine C14:0, carnitine C16:0, carnitine C18:0, and carnitine C18:1.

[0034] This invention analyzes the metabolome of patients with hypertrophic cardiomyopathy and those with left ventricular hypertrophy caused by non-hypertrophic cardiomyopathy in a deduced cohort. The results show that carnitine C16:2, carnitine C14:0, carnitine C16:0, carnitine C18:0, and carnitine C18:1 are differentially expressed in the plasma of both patients with and without hypertrophic cardiomyopathy. Receiver operating characteristic (ROC) curve analysis demonstrates that carnitine C16:2, carnitine C14:0, carnitine C16:0, carnitine C18:0, and carnitine C18:1 exhibit excellent predictive power, with areas under the curve (AUC) of 0.94, 0.94, 0.91, 0.82, and 0.79, respectively. Furthermore, this invention utilizes a validation cohort for testing. When carnitine C16:2, carnitine C14:0, carnitine C16:0, carnitine C18:0, and carnitine C18:1 are used as biomarkers, the area under the curve (AUC) reaches 0.88, 1.00, 0.91, 0.97, and 0.83, respectively. Therefore, it can be determined that using one or more of carnitine C16:2, carnitine C14:0, carnitine C16:0, carnitine C18:0, and carnitine C18:1 can accurately distinguish between left ventricular hypertrophy caused by hypertrophic cardiomyopathy and non-hypertrophic cardiomyopathy, demonstrating high specificity and sensitivity.

[0035] Therefore, the application of the biomarkers described in the above technical solution in the preparation of products that differentiate between hypertrophic cardiomyopathy and left ventricular hypertrophy also falls within the scope of protection of this invention; the left ventricular hypertrophy referred to is left ventricular hypertrophy caused by non-hypertrophic cardiomyopathy. As one embodiment, the product includes a reagent kit.

[0036] The present invention also provides a kit for distinguishing between hypertrophic cardiomyopathy and left ventricular hypertrophy, the kit comprising reagents for detecting the levels of the biomarkers described in the above technical solution; the left ventricular hypertrophy being left ventricular hypertrophy caused by non-hypertrophic cardiomyopathy.

[0037] This invention does not have strict requirements on the types of other components in the kit; conventional selection is sufficient. Using the kit described in this invention, it is only necessary to detect the levels of one or more of carnitine C16:2, carnitine C14:0, carnitine C16:0, carnitine C18:0, and carnitine C18:1 in the subject's plasma to accurately distinguish between left ventricular hypertrophy caused by hypertrophic cardiomyopathy and non-hypertrophic cardiomyopathy, without the need for gene testing.

[0038] The present invention also provides biomarkers associated with hypertrophic cardiomyopathy, including one or more of pyridoxine phosphate, itoric acid, adenosine monophosphate, adenosine diphosphate, and adenosine triphosphate.

[0039] In one embodiment, the pyridoxine phosphate, itoric acid, adenosine monophosphate, adenosine diphosphate, and adenosine triphosphate are respectively pyridoxine phosphate, itoric acid, adenosine monophosphate, adenosine diphosphate, and adenosine triphosphate in plasma.

[0040] In one embodiment, the marker may be a combination of two or more of pyridoxine phosphate, itoric acid, adenosine monophosphate, adenosine diphosphate, and adenosine triphosphate; in another embodiment, the marker may be a combination of three or more of pyridoxine phosphate, itoric acid, adenosine monophosphate, adenosine diphosphate, and adenosine triphosphate; in yet another embodiment, the marker may be a combination of four or more of pyridoxine phosphate, itoric acid, adenosine monophosphate, adenosine diphosphate, and adenosine triphosphate; and in yet another embodiment, the marker may be pyridoxine phosphate, itoric acid, adenosine monophosphate, adenosine diphosphate, and adenosine triphosphate.

[0041] This invention analyzes the metabolomes of hypertrophic cardiomyopathy (HCM) patients and healthy individuals in a deduced cohort. The results show that pyridoxine phosphate, itoric acid, adenosine monophosphate (AMS), AMS diphosphate (ADS), and ADS triphosphate are differentially expressed in both groups. Receiver operating characteristic (ROC) curve analysis demonstrates that pyridoxine phosphate, itoric acid, AMS, ADS, and ADS exhibit excellent predictive power. Furthermore, validation cohort analysis confirms that one or more of these substances can accurately distinguish between HCM patients and healthy individuals, providing high specificity and sensitivity for the diagnosis of HCM.

[0042] Therefore, the application of the biomarkers described in the above technical solution in products for diagnosing hypertrophic cardiomyopathy in the preparation area also falls within the protection scope of this invention. As one embodiment, the product includes a reagent kit.

[0043] The present invention also provides a kit for diagnosing hypertrophic cardiomyopathy, the kit comprising reagents for detecting the levels of the biomarkers described in the above-described technical solutions.

[0044] This invention does not have strict requirements on the types of other components in the kit; conventional selection is sufficient. Using the kit described in this invention, it is only necessary to detect the levels of one or more of pyridoxine phosphate, itoric acid, adenosine monophosphate, adenosine diphosphate, and adenosine triphosphate in the plasma of the subject to accurately distinguish between patients with hypertrophic cardiomyopathy and healthy individuals. Diagnosis of hypertrophic cardiomyopathy does not require gene testing, and it exhibits high specificity and sensitivity.

[0045] The present invention also provides biomarkers associated with left ventricular hypertrophy, including one or more of lysine, methylglutamic acid, acetylproline, malic semialdehyde and citric acid; wherein the left ventricular hypertrophy is left ventricular hypertrophy caused by non-hypertrophic cardiomyopathy.

[0046] In one embodiment, the lysine group, methylglutamic acid, acetylproline, malic acid semialdehyde, and citric acid are respectively lysine group, methylglutamic acid, acetylproline, malic acid semialdehyde, and citric acid in blood plasma.

[0047] In one embodiment, the marker may be a combination of two or more of lysine, methylglutamic acid, acetylproline, malic semialdehyde, and citric acid; in another embodiment, the marker may be a combination of three or more of lysine, methylglutamic acid, acetylproline, malic semialdehyde, and citric acid; in yet another embodiment, the marker may be a combination of four or more of lysine, methylglutamic acid, acetylproline, malic semialdehyde, and citric acid; and in yet another embodiment, the marker may be lysine, methylglutamic acid, acetylproline, malic semialdehyde, and citric acid.

[0048] This invention analyzes the metabolomes of patients with left ventricular hypertrophy (LVH) caused by non-hypertrophic cardiomyopathy (NSCHD) and healthy individuals in a deduced cohort. The results show that lysine, methylglutamate, acetylproline, malic acid semialdehyde, and citrate are differentially expressed in both groups. Receiver operating characteristic (ROC) curve analysis demonstrates that lysine, methylglutamate, acetylproline, malic acid semialdehyde, and citrate exhibit excellent predictive power. Furthermore, validation cohort testing confirms that using one or more of these biomarkers as markers can accurately diagnose LVH caused by non-hypertrophic cardiomyopathy in both patients and healthy individuals, demonstrating high specificity and sensitivity.

[0049] This invention also provides the application of the biomarkers described in the above-mentioned technical solution in the preparation of products for diagnosing left ventricular hypertrophy; wherein the left ventricular hypertrophy is caused by non-hypertrophic cardiomyopathy. As one embodiment, the product includes a reagent kit.

[0050] The present invention also provides a kit for diagnosing left ventricular hypertrophy, the kit comprising reagents for detecting the levels of the biomarkers described in the above technical solution; the left ventricular hypertrophy is left ventricular hypertrophy caused by non-hypertrophic cardiomyopathy.

[0051] This invention does not have strict requirements on the types of other components in the kit; conventional selection is acceptable. Using the kit described in this invention, it is only necessary to detect the levels of one or more of lysine, methylglutamic acid, acetylproline, malic semialdehyde, and citric acid in the plasma of the subject to accurately distinguish between patients with hypertrophic cardiomyopathy and healthy individuals. Diagnosis of hypertrophic cardiomyopathy does not require gene testing, and it exhibits high specificity and sensitivity.

[0052] To further illustrate the present invention, the metabolic markers for distinguishing hypertrophic cardiomyopathy and left ventricular hypertrophy provided by the present invention and their applications are described in detail below with reference to the accompanying drawings and embodiments. However, these descriptions should not be construed as limiting the scope of protection of the present invention.

[0053] Example 1

[0054] Sample collection

[0055] The inventors' team collected data from 720 individuals at Fuwai Hospital, Chinese Academy of Medical Sciences, including 441 patients with hypertrophic obstructive cardiomyopathy (HCM), 160 patients with left ventricular hypertrophy (LVH) not caused by HCM, and 119 normal controls (NC). The diagnostic criteria for obstructive HCM were based on the 2024 ACC / AHA Guidelines for Primary Prevention of Cardiovascular Disease and the 2023 ESC Guidelines, as follows: echocardiography showing a maximum left ventricular wall thickness ≥15 mm. Patients who had previously undergone septal myotomy and alcohol septal ablation were excluded. Clinical examination and echocardiography showed no cardiac disease in all normal controls. To minimize metabolite degradation, fasting blood samples were processed into frozen plasma within 1 hour. Whole blood was centrifuged at 4000 rpm for 10 minutes at 4°C, and the plasma supernatant was collected and aliquoted into 0.2 mL Eppendorf tubes (70 μL plasma per tube). The plasma was immediately quenched in liquid nitrogen and stored at -80°C until analysis. This study was approved by the Ethics Committee of Fuwai Hospital and conducted in accordance with the Declaration of Helsinki, 1964. All individuals participating in this study provided written informed consent. The clinical characteristics of the subjects are shown in Table 1.

[0056] Table 1 Clinical characteristics of the subjects

[0057]

[0058]

[0059] Note: Continuous variables are represented by the median (25th-75th percentile).

[0060] Example 2

[0061] Metabolomics analysis of plasma samples

[0062] 1. Equal volumes of plasma samples from each subject in the derivation cohort of Example 1 were mixed, extracted, centrifuged, dried, and redissolved before LC-MS analysis. The specific steps are as follows: Targeted metabolomics methods were performed using a Vanquish ultra-high performance liquid chromatography system coupled with a Q-Exactive HF mass spectrometer (Thermo Fisher Scientific). Gradient separation was performed using an ACQUITYBEHAmide column (150 × 2.1 mm, 1.7 μm, Waters). Solvent A: 95% water + 5% acetonitrile; Solvent B: 5% water + 95% acetonitrile. The gradient settings were as follows: 0–1.5 min, 5% A; 1.5–10 min, 5–35% A; 10–19 min, 35–70% A; 19–23.5 min, 70% A; 23.5–25 min, 70–5% A; 25–30 min, 5% A. Data were acquired in fullMS-ddMS2 mode (top five negative ions) and processed using Compound Discoverer version 3.3 software (Thermo Fisher Scientific). The process included deconvolution, peak alignment, extraction, and annotation. The following mass spectrometry parameters were set: scan mode, MS / MS; resolution 30,000, normalized collision energies 20, 40, and 60 eV. Source ionization parameters were: spray voltage 3.5 kV for electrospray positive ions (ESI+), capillary temperature 320 °C, sheath gas 40 °C, and auxiliary gas 15 °C. LC-MS analysis identified 406 metabolites, including amino acids, organic acids, nucleotides, acylcarnitines, and carbohydrates, providing a comprehensive metabolic profile.

[0063] 2. General metabolic characteristics of plasma from HCM patients, LVH patients, and normal controls

[0064] Using plasma samples from each patient in the cohort derived in Example 1 as test samples, the following tests were performed:

[0065] (1) Use Version 15.0 of the software (Umetrics) Orthogonal partial least squares discriminant analysis (OPLS-DA) was performed in Sweden. Unit variance (UV) scaling was performed before multivariate analysis to establish the OPLS-DA model. The results showed that there were significant metabolite differences between HCM and LVH, HCM and NC, and LVH and NC.

[0066] (2) The performance of the OPLS-DA model was evaluated using R²Y and Q² intercepts, and the consistency of the fit was assessed using cross-validation analysis of variance (CV-ANOVA). The results showed that the variance of all predictions (HCM vs. LVH, R²Y = 0.972; HCM vs. NC, R²Y = 0.974; LVH vs. NC, R²Y = 0.951), predictive power (HCM vs. LVH, Q² = 0.952; HCM vs. NC, Q² = 0.954; LVH vs. NC, Q² = 0.914), and CV-ANOVA (HCM vs. LVH, P < 0.001; HCM vs. NC, P < 0.001; LVH vs. NC, P < 0.001) values ​​indicate that the OPLS-DA model is robust and reliable.

[0067] (3) To prevent overfitting, a permutation test (n=200) was conducted, and the results showed that the OPLS-DA model did not overfit.

[0068] (4) Enrichment analysis and unsupervised hierarchical clustering analysis were performed using the Kyoto Encyclopedia of Genetics and Genomes (KEGG) database. Results showed that 83 differentially expressed metabolites were identified between HCM and LVH, 103 between HCM and NC, and 79 between LVH and NC (Mann-Whitney U test, FDR < 0.05 and |FC| > 2). KEGG pathway analysis revealed that differentially expressed metabolites between HCM and LVH, HCM and NC, and LVH and NC were enriched in arginine and proline metabolism, cysteine ​​and methionine metabolism, and histidine metabolism, respectively. Unsupervised hierarchical clustering analysis indicated that the metabolic characteristics of HCM differed significantly from the other two groups. In summary, metabolomics provides valuable insights into the etiological heterogeneity of HCM, LVH, and NC.

[0069] (5) Perform pairwise comparisons (HCM vs. LVH, HCM vs. NC, and LVH vs. NC) to screen biomarkers using the following steps: (1) False discovery rate (FDR) adjusted P-value < 0.05: 309, 321, and 335 metabolites met this criterion in the comparisons of HCM vs. LVH, HCM vs. NC, and LVH vs. NC, respectively. (2) |FC| > 2: After this step, 83, 103, and 79 metabolites remained in the comparisons of HCM vs. LVH, HCM vs. NC, and LVH vs. NC, respectively. (3) OPLS-DAVIP value > 1.5: Ultimately, 27, 39, and 16 metabolites were considered as potential biomarkers in the comparisons of HCM vs. LVH, HCM vs. NC, and LVH vs. NC, respectively.

[0070] 3. Biomarker identification to differentiate between HCM and LVH patients

[0071] The diagnostic performance of potential biomarkers in step 2 was evaluated using receiver operating characteristic (ROC) curves and box plot analysis. The results showed that long-chain acylcarnitines exhibited particularly strong and consistent diagnostic performance in distinguishing between HCM and LVH. Specifically, C16:2carnitine, C14:0carnitine, C16:0carnitine, C18:0carnitine, and C18:1carnitine showed excellent predictive power, with areas under the curve (AUC) reaching 0.94, 0.94, 0.91, 0.82, and 0.79, respectively. Figure 1 and Figure 2 Compared with non-nociceptive (NC), pyridoxine phosphate, itaconic acid, adenosine monophosphate (AMP), adenosine diphosphate (ADP), and adenosine triphosphate (ATP) showed excellent predictive power in HCM patients, with areas under the curve (AUC) of 0.89, 0.90, 0.93, 0.95, and 0.99, respectively. Figure 3 and Figure 4 This indicates that HCM exhibits abnormal energy metabolism even in the absence of contractile dysfunction. The metabolic differences between LVH and NC are mainly focused on their effects on amino acid metabolism; lysidine, methylglutamate, acetylproline, succinate semialdehyde, and citric acid showed excellent predictive power, with areas under the curve (AUC) reaching 0.91, 0.97, 0.94, 0.91, and 0.94, respectively. Figure 5 and Figure 6 Therefore, plasma metabolomics can be used to differentiate between patients with hepatocellular carcinoma (HCM) and non-HCM-induced LVH, improving the accuracy of HCM differential diagnosis.

[0072] Example 3

[0073] Using plasma samples from each patient in the validation cohort of Example 1 as test samples, receiver operating characteristic (ROC) curve analysis and box plot analysis were performed according to the steps in Example 4. The results showed that C16:2 carnitine, C14:0 carnitine, C16:0 carnitine, C18:0 carnitine, and C18:1 carnitine exhibited excellent predictive performance, with areas under the curve (AUC) reaching 0.88, 1.00, 0.91, 0.97, and 0.83, respectively. Figure 7 and Figure 8 Carnitine C16:2, carnitine C14:0, carnitine C16:0, carnitine C18:0, and carnitine C18:1 were identified as markers for distinguishing LVH caused by HCM and non-HCM.

[0074] Pyridoxine phosphate, itaconic acid, adenosine monophosphate (AMP), adenosine diphosphate (ADP), and adenosine triphosphate (ATP) showed excellent predictive performance, with areas under the curve (AUC) of 0.89, 0.91, 0.95, 0.97, and 0.99, respectively. Figure 7 and Figure 8 Pyridoxine phosphate, itoric acid, adenosine monophosphate, adenosine diphosphate, and adenosine triphosphate have been identified as biomarkers that can differentiate HCM from healthy individuals and diagnose HCM.

[0075] Lysidine, methylglutamate, acetylproline, succinate semialdehyde, and citrulline showed excellent predictive performance, with areas under the curve (AUC) reaching 0.86, 1.00, 1.00, 1.00, and 0.60, respectively. Figure 7 and Figure 8 Lysine, methylglutamic acid, acetylproline, malic semialdehyde, and citric acid have been identified as biomarkers that can differentiate LVH from healthy individuals and diagnose LVH.

[0076] Although the above embodiments have provided a detailed description of the present invention, they are only some embodiments of the present invention, and not all embodiments. People can obtain other embodiments based on these embodiments without creative effort, and these embodiments all fall within the protection scope of the present invention.

Claims

1. Application of reagents for detecting biomarker expression levels in the preparation of kits to differentiate between hypertrophic cardiomyopathy and left ventricular hypertrophy; The biomarker was carnitine C16:0; The left ventricular hypertrophy mentioned refers to left ventricular hypertrophy caused by non-hypertrophic cardiomyopathy.

2. The application according to claim 1, characterized in that, The biomarker is a biomarker in plasma.

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