Adrenocortical carcinoma differential or diagnostic marker and use thereof

Abstract

The application relates to an adrenal cortex cancer differential or diagnostic marker and application thereof. The application finds that 5-hydroxytryptamine and 5-hydroxyindoleacetic acid are closely related to the occurrence of adrenal cortex cancer, and therefore first proposes that 5-hydroxytryptamine and / or 5-hydroxyindoleacetic acid are used as markers in the preparation of related products for identifying, diagnosing and screening adrenal cortex cancer. By using the compound as a marker for predicting the occurrence of adrenal cortex cancer, the early onset and the malignant degree of adrenal cortex cancer can be accurately and sensitively predicted and identified, so that the technical difficulty of diagnosing adrenal cortex cancer is reduced, and a brand-new objective index is provided for the identification, diagnosis, screening or drug efficacy evaluation of adrenal cortex cancer.

Description

Technical Field

[0001] This application relates to the field of biomedical technology, specifically to biomarkers for the identification or diagnosis of adrenocortical carcinoma and their applications. Background Technology

[0002] Adrenocortical carcinoma (ACC) is a malignant tumor that occurs in the adrenal cortex, with a clinical incidence of 0.5-2 per million people. It is characterized by high malignancy, aggressiveness, and a high rate of metastasis, resulting in a poor prognosis. Most patients with adrenocortical carcinoma survive for 4-30 months, with a 5-year overall survival rate of 16%-47%, while the 5-year survival rate for patients with advanced-stage cancer is only 5%-10%. Recent studies have shown a significant increasing incidence of adrenocortical carcinoma, accounting for approximately 2.4% of all adrenal neoplasia and 68.8% of all adrenal malignancies. Surgery is the most effective treatment for adrenocortical carcinoma, and complete tumor resection is currently the only potentially curative method, especially suitable for patients without extensive metastasis. However, due to the high malignancy and rapid progression of adrenocortical carcinoma, many patients present with tumor infiltration into surrounding tissues or distant metastasis, thus losing the opportunity for surgery. Early diagnosis and complete surgical resection of the tumor remain crucial for the treatment of adrenocortical carcinoma. Therefore, early and accurate diagnosis is particularly important for the treatment and prognosis of adrenocortical carcinoma. However, some adrenocortical adenomas (ACA) and adrenocortical carcinomas with difficult-to-define characteristics pose challenges to current conventional endocrine, imaging, and pathological diagnostic methods. The search for and discovery of novel biomarkers to assist clinicians in diagnosing adrenocortical carcinoma, assessing its severity, treatment effectiveness, and prognosis is also an urgent problem to be solved in the field of adrenocortical carcinoma diagnosis and treatment. This application aims to find a small molecule compound to achieve rapid identification of adrenocortical carcinoma. Summary of the Invention

[0003] To address the aforementioned technical problems, some embodiments of this application provide a biomarker for the identification, diagnosis, screening, or efficacy evaluation of adrenocortical carcinoma and its application.

[0004] The technical solution is as follows:

[0005] A biomarker for the identification, diagnosis, screening, or efficacy evaluation of adrenocortical carcinoma, said biomarker comprising 5-hydroxytryptamine and / or 5-hydroxyindoleacetic acid.

[0006] The application of reagents for detecting the content of the markers in samples in the preparation of products for differentiating adrenocortical carcinoma and adrenocortical adenoma.

[0007] The use of reagents for detecting the content of the biomarkers in samples in the preparation of products for the diagnosis and / or auxiliary diagnosis of adrenocortical carcinoma.

[0008] Using 5-hydroxytryptamine and / or 5-hydroxyindoleacetic acid as biomarkers associated with adrenocortical carcinoma provides an easily detectable and objective indicator for the identification, diagnosis, and / or auxiliary diagnosis of adrenocortical carcinoma, characterized by high targeting, stability, and sensitivity.

[0009] The use of reagents for detecting the content of the biomarkers in samples in the preparation of products for screening and / or assisting in the screening of adrenocortical carcinoma.

[0010] Using 5-hydroxytryptamine and / or 5-hydroxyindoleacetic acid as biomarkers associated with adrenocortical carcinoma in screening and / or adjuvant screening for adrenocortical carcinoma can relatively accurately predict whether adrenocortical carcinoma occurs and its progression, providing a convenient and non-invasive screening method for adrenocortical carcinoma.

[0011] The application of reagents for detecting the content of the biomarkers in samples in the preparation of products for evaluating the efficacy of adrenocortical carcinoma treatment.

[0012] In one embodiment, the 5-hydroxyindoleacetic acid content is reduced in patients with adrenocortical adenoma compared to patients or healthy individuals.

[0013] In one embodiment, the 5-hydroxytryptamine level is elevated in patients with adrenocortical adenoma compared to patients or healthy individuals.

[0014] In one embodiment, the product includes one or more of test strips, reagent kits, chips, and devices.

[0015] In one embodiment, the product includes a medical device.

[0016] In one embodiment, the sample includes serum, plasma, or whole blood.

[0017] In one embodiment, the reagent for detecting the content of the marker in the sample includes one or more detection reagents selected from chromatography, spectroscopy, mass spectrometry, nuclear magnetic resonance, and chemical analysis.

[0018] In one embodiment, the reagent for detecting the content of the marker in the sample includes reagents for liquid chromatography-mass spectrometry analysis.

[0019] A product for the identification, diagnosis, screening, or efficacy evaluation of adrenocortical carcinoma, the product comprising a reagent for detecting the biomarker in a sample.

[0020] In one embodiment, the product includes a medical device. The medical device works by detecting the levels of 5-hydroxytryptamine and / or 5-hydroxyindoleacetic acid (5-HT) in a sample using 5-hydroxytryptamine and / or 5-hydroxyindoleacetic acid as markers, thereby enabling the identification, diagnosis, screening, or efficacy evaluation of adrenocortical carcinoma. Using this medical device allows for convenient and non-invasive diagnosis or efficacy evaluation of adrenocortical carcinoma with high sensitivity.

[0021] A computer-based identification, diagnosis, or screening system or device, comprising:

[0022] The result determination unit is used to analyze the level of the markers in the detected samples and output the results, wherein the markers include 5-hydroxyindoleacetic acid.

[0023] In one embodiment, the marker includes 5-hydroxytryptamine.

[0024] In one embodiment, the sample is selected from serum, plasma, or whole blood.

[0025] In one embodiment, a detection unit is also included for detecting the level of a marker in the sample.

[0026] In one embodiment, the result determination unit includes an input portion for inputting the level of the marker.

[0027] In one embodiment, the result determination unit further includes an analysis section for analyzing whether the subject is a patient with adrenocortical carcinoma based on the level of the biomarker.

[0028] In one embodiment, the result determination unit further includes an output section for outputting the analysis results of the analysis section.

[0029] Compared with traditional technologies, this application has the following advantages:

[0030] This application found that plasma serotonin and 5-hydroxyindoleacetic acid (5-HT) levels are closely related to the occurrence of adrenocortical carcinoma. Based on blood samples from three groups—a healthy control group, an adrenocortical adenoma group, and an adrenocortical carcinoma group—it was found that plasma serotonin levels were significantly elevated in patients with adrenocortical adenoma, and further elevated in patients with adrenocortical carcinoma. Plasma 5-HT levels were significantly decreased in patients with adrenocortical adenoma, and further decreased in patients with adrenocortical carcinoma. Significant differences were found in the levels of serotonin and 5-hydroxyindoleacetic acid among the three groups. Therefore, this study proposes for the first time the use of serotonin and / or 5-hydroxyindoleacetic acid as biomarkers in the preparation of products for the identification, diagnosis, and screening of adrenocortical carcinoma. Using this compound as a biomarker to predict the occurrence of adrenocortical carcinoma can accurately and sensitively predict and identify the early onset and malignancy of adrenocortical carcinoma, thereby reducing the technical difficulty of diagnosing adrenocortical carcinoma. This provides a new objective indicator for the identification, diagnosis, screening, or drug efficacy evaluation of adrenocortical carcinoma, and offers a new approach to assessing the severity, treatment effect, and prognosis of adrenocortical carcinoma. Attached Figure Description

[0031] To more clearly illustrate the technical solutions in the embodiments of this application and to more completely understand this application and its beneficial effects, the drawings used in the description of the embodiments will be briefly introduced below. Obviously, the drawings described below are only some embodiments of this application. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0032] Figure 1 PCA was used to visualize the differences among the three groups for comparative analysis of the metabolomics profiles among the three groups.

[0033] Figure 2 Heatmap of differentially metabolites in the plasma of patients with adrenocortical carcinoma.

[0034] Figure 3 The figure shows a comparison of the levels of 5-hydroxytryptamine and its metabolite 5-hydroxyindoleacetic acid in the plasma of patients with adrenocortical carcinoma, adrenocortical adenoma, and healthy individuals in the examples (***P<0.001).

[0035] Figure 4 ROC curves of plasma 5-hydroxytryptamine and its metabolite 5-hydroxyindoleacetic acid levels in the diagnosis of adrenocortical carcinoma in patients and healthy controls.

[0036] Figure 5ROC curves of plasma 5-hydroxytryptamine and its metabolite 5-hydroxyindoleacetic acid levels in the diagnosis of adrenocortical carcinoma and adrenocortical adenoma. Detailed Implementation

[0037] To make the above-mentioned objectives, features, and advantages of this application more apparent and understandable, a detailed description of specific embodiments of this application is provided below. Many specific details are set forth in the following description to provide a thorough understanding of this application. However, this application can be implemented in many other ways different from those described herein, and those skilled in the art can make similar modifications without departing from the spirit of this application. Therefore, this application is not limited to the specific embodiments disclosed below.

[0038] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this application belongs. The terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the application.

[0039] In this document, the term "and / or" includes any and all combinations of one or more of the related listed items.

[0040] In order to find novel biomarkers for adrenocortical carcinoma, the inventors of this application used non-targeted metabolomics technology to analyze the levels of 488 small metabolic molecules in the plasma of patients with adrenocortical carcinoma, patients with adrenocortical adenoma, and age- and sex-matched healthy controls. They found that the levels of various metabolites in patients with adrenocortical carcinoma changed significantly. Among these differentially expressed metabolites, the small molecule metabolite 5-hydroxytryptamine (5-HT) and its metabolite 5-hydroxyindoleacetic acid (5-HIA) showed significant differences between patients with adrenocortical carcinoma, patients with adrenocortical adenoma, and healthy controls. This suggests that 5-HT and 5-HIA are closely related to the occurrence of adrenocortical carcinoma and can be used as biomarkers for the identification, diagnosis, auxiliary diagnosis, screening, and / or adjuvant therapy of adrenocortical carcinoma.

[0041] 5-Hydroxytryptamine, abbreviated as 5-HT, has the chemical formula C5. 10 H 12N₂O, with a molecular weight of 176.22, is an important neurotransmitter with multiple physiological regulatory functions. It belongs to the class of biogenic amines and is widely found in mammalian tissues. Serotonin (5-hydroxytryptamine) is mainly found in platelets and neurons of the central nervous system, synthesized from tryptophan through multiple biosynthetic steps. 5-Hydroxyindoleacetic acid (5-HIA) is the end product of the tryptophan-5-hydroxytryptamine metabolic pathway, converted from 5-hydroxytryptamine by monoamine oxidase. Besides enterochromaffin cells synthesizing 5-hydroxytryptamine, some tumor cells and immune cells can also secrete 5-hydroxytryptamine. These cells have different 5-hydroxytryptamine receptors on their surface, and 5-hydroxytryptamine acts on different receptors to exert various biological effects. To date, there are no publicly available reports on the correlation between 5-hydroxytryptamine and its metabolite 5-hydroxyindoleacetic acid levels and adrenocortical carcinoma. The structural formulas of 5-hydroxytryptamine and its metabolite 5-hydroxyindoleacetic acid are as follows:

[0042] 5-Hydroxytryptamine structural formula:

[0043]

[0044] 5-Hydroxyindoleacetic acid structural formula:

[0045]

[0046] One embodiment of this application provides the use of 5-hydroxytryptamine and / or 5-hydroxyindoleacetic acid as markers in the preparation of the following products:

[0047] a. Products used for the identification, diagnosis, and / or auxiliary diagnosis of adrenocortical carcinoma.

[0048] b. Products used for screening and / or assisting in the screening of adrenocortical carcinoma.

[0049] c. Products used for evaluating the efficacy of drugs for adrenocortical carcinoma.

[0050] Among them, the identification, diagnosis and / or auxiliary diagnosis of adrenocortical carcinoma refers to the identification, diagnosis and / or auxiliary diagnosis of whether adrenocortical carcinoma has occurred by measuring the levels of 5-hydroxytryptamine and its metabolite 5-hydroxyindoleacetic acid in plasma.

[0051] This embodiment proposes for the first time the application of 5-hydroxytryptamine (5-HT) and / or 5-hydroxyindoleacetic acid (5-HICA) as biomarkers in the diagnosis of adrenocortical carcinoma and related fields. For example, 5-HT and / or 5-HICA can be used as biomarkers in the preparation of products for diagnosing adrenocortical carcinoma, thereby reducing the difficulty of diagnosis. Furthermore, using 5-HT and / or 5-HICA as biomarkers for adrenocortical carcinoma provides an easily detectable and objective indicator for the identification, diagnosis, and screening of adrenocortical carcinoma, and it exhibits high targeting, stability, and sensitivity.

[0052] In a specific example, the product mentioned above for the identification, diagnosis, and screening of adrenocortical carcinoma is a diagnostic reagent, which may include diagnostic test strips, reagent kits, and diagnostic chips.

[0053] In one specific example, the test sample for the above-mentioned diagnostic reagent is plasma, and the diagnostic reagent is used to detect the levels of 5-hydroxytryptamine and / or 5-hydroxyindoleacetic acid in the plasma.

[0054] It is understood that products that detect the levels of 5-hydroxytryptamine and / or 5-hydroxyindoleacetic acid in plasma can be used to prepare products for the identification, diagnosis, and / or auxiliary diagnosis of adrenocortical carcinoma; or, they can be used to prepare products for screening and / or auxiliary screening of adrenocortical carcinoma. Therefore, the application of products that detect the levels of 5-hydroxytryptamine and / or 5-hydroxyindoleacetic acid in plasma in the identification, diagnosis, and screening of adrenocortical carcinoma also falls within the scope of protection of this application.

[0055] One embodiment of this application also provides a medical device for the identification, diagnosis, screening, or efficacy evaluation of adrenocortical carcinoma, which uses 5-hydroxytryptamine and its metabolite 5-hydroxyindoleacetic acid as markers to detect the levels of 5-hydroxytryptamine and / or 5-hydroxyindoleacetic acid in a sample.

[0056] The aforementioned medical devices used for the identification, diagnosis, screening, or efficacy evaluation of adrenocortical carcinoma include diagnostic test strips, reagent kits, diagnostic chips, and related testing equipment.

[0057] In one specific example, the test sample for the aforementioned medical device is plasma.

[0058] This application is the first to propose the use of 5-hydroxytryptamine and / or 5-hydroxyindoleacetic acid (5-HT) as biomarkers in the preparation of products for the identification, diagnosis, screening, or efficacy evaluation of adrenocortical carcinoma. It is readily understood that corresponding reagents capable of detecting the concentration or level of 5-HT and its metabolite 5-hydroxyindoleacetic acid can also be used to prepare products for the identification, diagnosis, screening, or efficacy evaluation of adrenocortical carcinoma, and are therefore also within the scope of protection of this application. Furthermore, any product used for the identification, diagnosis, screening, or efficacy evaluation of adrenocortical carcinoma based on this application, as long as it uses 5-HT and its metabolite 5-hydroxyindoleacetic acid as biomarkers and detects the level of 5-HT and its metabolite 5-hydroxyindoleacetic acid in the sample, falls within the scope of protection of this application.

[0059] The embodiments of this application will be described in detail below with reference to examples. It should be understood that these embodiments are for illustrative purposes only and are not intended to limit the scope of this application. For experimental methods in the following embodiments where specific conditions are not specified, please refer to the guidelines given in this application, or follow experimental manuals or conventional conditions in the art, or follow the conditions recommended by the manufacturer, or refer to experimental methods known in the art.

[0060] In the specific embodiments described below, the measurement parameters involving raw material components may have slight deviations within the weighing accuracy range unless otherwise specified. Temperature and time parameters are subject to acceptable deviations due to instrument testing accuracy or operational precision.

[0061] Example 1

[0062] Using healthy controls (HC) and patients with adrenocortical carcinoma (ACC) and adrenocortical adenoma (ACA) as subjects, this study revealed the close relationship between plasma serotonin and its metabolite 5-hydroxyindoleacetic acid levels and adrenocortical carcinoma.

[0063] 1. Subjects:

[0064] Subject population: Subjects were patients treated at Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, and recruited healthy individuals.

[0065] Inclusion and exclusion criteria for patients with adrenocortical carcinoma and adrenocortical adenoma: (1) Inclusion criteria: 1) Age ≥ 18 years. 2) Inpatients with a confirmed diagnosis of adrenocortical carcinoma or adrenocortical adenoma, with the diagnosis based on pathological results. (2) Exclusion criteria: 1) Postoperative patients. 2) Patients treated with mitotane, ketoconazole or mifepristone.

[0066] A total of 42 patients with adrenocortical carcinoma, 56 patients with adrenocortical adenoma, and 54 healthy controls were selected (matched by age, sex, and disease group). All subjects signed informed consent forms.

[0067] 2. Preparation of blood samples

[0068] (1) Collection and storage of blood samples: Venous blood was collected from fasting patients and healthy controls. Ethylenediamine tetraacetic acid (EDTA) was used as an anticoagulant, and the blood was centrifuged at 5000 r / min for 10 minutes at 4°C within 30 minutes of collection. The supernatant was transferred to cryovials, rapidly frozen in liquid nitrogen, and then stored at -80°C. All sample transport was performed on dry ice to ensure that the samples were not subjected to repeated freeze-thaw cycles before testing.

[0069] (2) Thaw the sample on an ice bath, transfer 50 μL to a 1.5 mL tube, add 150 μL of ultrapure water, and vortex for 30 seconds to mix. Add 400 μL of acetonitrile and vortex again for 30 seconds to mix. Centrifuge the sample at 14000 g for 10 minutes to remove the protein precipitate. Transfer the supernatant to a 10 mL glass tube and evaporate to dryness using a container evaporator at room temperature. Dissolve the residue in 200 μL of a mixed solution (2% acetonitrile), filter the solution using an ultracentrifuge filter to remove molecules with a molecular weight greater than 10 kDa, collect the supernatant, and analyze it using liquid chromatography-mass spectrometry (LC-MS).

[0070] 3. Analytical conditions for liquid chromatography-mass spectrometry:

[0071] (1) Chromatographic conditions:

[0072] Chromatographic column: Waters HSS C18 column (3.0×100mm, 1.7μm); Mobile phase: Phase A: water (containing 0.1% formic acid); Phase B: acetonitrile; Gradient elution program: 0-1 min, 2% solvent B; 1-3 min, 2%-15% solvent B; 3-6 min, 15%-50% solvent B; 6-9 min, 50%-95% solvent B; 9-9.1 min, 95%-100% solvent B; 9.1-12 min, 100% solvent B; 12-12.1 min, 100%-2% solvent B; and 12-17 min, 2% solvent B. Flow rate: 0.5 mL / min; Column temperature: 45℃; Injection volume: 5 μL; Injector temperature: 4℃.

[0073] (2) Mass spectrometry conditions

[0074] MS and MS / MS spectra were acquired using a data-dependent acquisition mode. The 10 most abundant ions were fragmented by MS / MS at collision energies of 35 ± 15 eV.

[0075] 4. Statistical Analysis:

[0076] PCA was used to visualize the differences among the three groups for comparative analysis of their metabolomics profiles.

[0077] Using the LC-MS detection results from step 3, software was used to analyze and plot a comparison graph of 5-hydroxytryptamine and 5-hydroxyindoleacetic acid levels in the plasma of adrenocortical carcinoma patients and healthy controls (HC), as well as ROC curves for diagnosing adrenocortical carcinoma based on plasma 5-hydroxytryptamine and 5-hydroxyindoleacetic acid levels.

[0078] 5. Results:

[0079] Figure 1 PCA was used to visualize the differences among the three groups for comparative analysis of their metabolomics profiles. Each group exhibited significantly different clusters, indicating that the metabolomics characteristics of the three groups were clearly different.

[0080] Figure 2 This is a heatmap of differential metabolites in the plasma of patients with adrenocortical carcinoma, reflecting the overall distribution of small molecules in the plasma. Columns represent samples, rows represent metabolites, the clustering tree on the left is the differential metabolite clustering tree, and the top is the sample clustering tree. Gradient colors indicate quantitative values; the redder the color, the higher the expression level, and the bluer the color, the lower the expression level. As shown in the figure, the small molecules 5-hydroxytryptamine and 5-hydroxyindoleacetic acid exhibit significant changes in the plasma of patients with adrenocortical carcinoma.

[0081] Figure 3 The box plots illustrate the logarithmic and distributional differences in plasma serotonin and 5-hydroxyindoleacetic acid (5-HT) concentrations among the healthy control group, the adrenocortical adenoma group, and the adrenocortical carcinoma patient group, with each point representing one sample. As shown in the figure, the plasma serotonin concentration in ACC patients was significantly higher than that in the adrenocortical adenoma group and the healthy population, while the 5-HT concentration was significantly lower in the adrenocortical adenoma group and the healthy population. Statistical p-values ​​were all less than 0.001 (generally considered to be less than 0.05 to indicate statistical significance), further demonstrating the reliability and high reproducibility of the results.

[0082] Figure 4 The ROC curves of plasma serotonin and 5-hydroxyindoleacetic acid (5-HT) levels in the diagnosis of adrenocortical carcinoma in patients and healthy controls are presented, representing a comprehensive indicator of continuous variables reflecting sensitivity and specificity. Plotting sensitivity (true positive rate) on the Y-axis and 1-specificity (false positive rate) on the X-axis, the areas under the ROC curves (AUCs) were 0.843 and 0.840, respectively, both greater than 0.5, indicating good diagnostic efficacy; the p-values ​​were both <0.0001, indicating good statistical significance. Specifically, the optimal cutoff value for serotonin showed a sensitivity of 0.667 and a specificity of 0.963; the optimal cutoff value for 5-HT showed a sensitivity of 0.852 and a specificity of 0.81.

[0083] Figure 5 The ROC curves of plasma serotonin and 5-hydroxyindoleacetic acid (5-HT) levels in the diagnosis of adrenocortical carcinoma and adrenocortical adenoma are shown. The areas under the ROC curves (AUC) were 0.775 and 0.892, respectively, both greater than 0.5, indicating good diagnostic efficacy; the P-value was <0.0001, indicating good statistical significance. Specifically, the optimal cutoff value for serotonin had a sensitivity of 0.667 and a specificity of 0.893; the optimal cutoff value for 5-HT had a sensitivity of 0.875 and a specificity of 0.833.

[0084] The results indicate that plasma 5-hydroxytryptamine and 5-hydroxyindoleacetic acid levels can serve as biomarkers for the clinical diagnosis of adrenocortical carcinoma.

[0085] In summary, the research results of this application found that 5-hydroxytryptamine and 5-hydroxyindoleacetic acid are closely related to the occurrence of adrenocortical carcinoma. For the first time, it is proposed to use 5-hydroxytryptamine and 5-hydroxyindoleacetic acid as biomarkers in the preparation of products for the identification, diagnosis, and screening of adrenocortical carcinoma. This provides a new objective indicator for the identification, diagnosis, screening, or drug efficacy evaluation of adrenocortical carcinoma, and offers a new approach to assessing the severity, treatment effect, and prognosis of adrenocortical carcinoma.

[0086] The technical features of the above embodiments can be combined in any way. For the sake of brevity, not all possible combinations of the technical features in the above embodiments are described. However, as long as there is no contradiction in the combination of these technical features, they should be considered to be within the scope of this specification.

[0087] The embodiments described above are merely illustrative of several implementation methods of this application, and while the descriptions are relatively specific and detailed, they should not be construed as limiting the scope of the invention patent. It should be noted that those skilled in the art can make various modifications and improvements without departing from the concept of this application, and these all fall within the protection scope of this application. Therefore, the protection scope of this patent application should be determined by the appended claims, and the specification can be used to interpret the content of the claims.

Claims

1. The use of a reagent for detecting the content of biomarkers in a sample in the preparation of products for differentiating adrenocortical carcinoma and adrenocortical adenoma, wherein the biomarkers include 5-hydroxytryptamine and / or 5-hydroxyindoleacetic acid.

2. The use of reagents for detecting the content of biomarkers in samples in the preparation of products for the diagnosis and / or auxiliary diagnosis of adrenocortical carcinoma, wherein the biomarkers include 5-hydroxyindoleacetic acid.

3. The application according to claim 2, characterized in that, The markers also include 5-hydroxytryptamine.

4. The use of reagents for detecting the content of biomarkers in samples in the preparation of products for screening and / or assisting in the screening of adrenocortical carcinoma, wherein the biomarkers include 5-hydroxyindoleacetic acid.

5. The application according to claim 4, characterized in that, The markers also include 5-hydroxytryptamine.

6. The application according to any one of claims 1-5, characterized in that, Compared to patients with adrenocortical adenoma or healthy individuals, the levels of the aforementioned 5-hydroxyindoleacetic acid are reduced in patients with adrenocortical carcinoma; and / or, Compared to patients with adrenocortical adenoma, the levels of serotonin are elevated in patients with adrenocortical carcinoma.

7. The application according to any one of claims 1-5, characterized in that, The products include one or more of test strips, reagent kits, chips, and devices.

8. The application according to any one of claims 1-5, characterized in that, The products include medical devices.

9. The application according to any one of claims 1-5, characterized in that, The samples include serum, plasma, or whole blood.

10. The application according to any one of claims 1-5, characterized in that, The reagents used to detect the content of the marker in the sample include one or more reagents selected from chromatography, spectroscopy, mass spectrometry, nuclear magnetic resonance, and chemical analysis.

11. The application according to any one of claims 1-5, characterized in that, The reagents used to detect the content of the markers in the sample include reagents for liquid chromatography-mass spectrometry analysis.

12. A computer-based identification, diagnosis, or screening system or device, characterized in that, include: The result determination unit is used to analyze the level of the markers in the detected samples and output the results, wherein the markers include 5-hydroxyindoleacetic acid; The result determination unit includes an input section for inputting the level of the marker; The result determination unit also includes an analysis section, which is used to analyze whether the subject is a patient with adrenocortical carcinoma based on the level of the biomarker; The result determination unit also includes an output section for outputting the analysis results of the analysis section.

13. The system or apparatus according to claim 12, characterized in that, The markers include 5-hydroxytryptamine.

14. The system or apparatus according to claim 12 or 13, characterized in that, The sample is selected from serum, plasma or whole blood.

15. The system or apparatus according to claim 12 or 13, characterized in that, It also includes a detection unit for detecting the level of markers in the sample.

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