Urine metabolism small molecule combination for early detection of lung cancer and application of urine metabolism small molecule combination
By detecting 2,3-pinenediol in urine as a biomarker, and using GC-MS technology to analyze the concentration of urine metabolites, the problem of early detection of lung cancer is solved, non-invasive and accurate lung cancer screening is achieved, and the diagnosis and treatment effect of high-risk populations is improved.
Patent Information
- Application Number
- CN202411941604.6
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2024-12-26
- Publication Date
- 2025-03-18
AI Technical Summary
The prior art is difficult to effectively conduct early detection of lung cancer, especially in high-risk groups, resulting in delayed diagnosis and poor treatment effect.
By detecting 2,3-pinenediol in urine as a biomarker, GC-MS technology is used to analyze the concentration of urine metabolites to achieve a non-invasive diagnosis of early lung cancer.
This method can effectively screen high-risk populations, improve the accuracy and sensitivity of early detection of lung cancer, and help improve the survival and cure rate of patients.
Smart Images
Figure CN119643751A_ABST
Abstract
Description
Technical Field
[0001] The present invention relates to the field of biomedicine technology, and in particular to a urine metabolic small molecule combination for early detection of lung cancer and an application thereof. Background Art
[0002] Lung cancer is the second leading cause of cancer and the leading cause of cancer death. Due to the lack of specific clinical symptoms and signs, lung cancer is often in the middle and late stages once discovered, and the treatment effect is limited. The use of low-dose computed tomography screening technology in high-risk groups can help diagnose lung cancer in its early stages. However, its high sensitivity makes false positive diagnostic results more likely to occur, and it is difficult to apply it to general screening for lung cancer in the short term. Therefore, early diagnosis of lung cancer is crucial, especially for screening high-risk groups who smoke, are exposed to smoke, oil fields, and toxic occupational workplaces.
[0003] Metabolomics mainly studies the changes in metabolic responses of biological systems under external stimulation and their reflection on the physiological and pathological conditions of the organism. Metabolomics can find tumor markers from the body's dynamic metabolic pathways, which is helpful for the early detection of tumors and the realization of non-invasive diagnosis of tumors.
[0004] The research object of metabolomics is the metabolites of organisms, such as body fluids, cell culture fluids, tissue extracts and tissues.
[0005] However, with continuous research, more valuable biomarkers have been found in urine through various methods, and urine has received increasing attention in the field of biomarker research.
[0006] Urine is the end product of the body's metabolism and can reflect the body's functional state and health level. By detecting the differential components in urine, we can analyze and judge the body's health status and find non-invasive detection methods for disease markers. In the absence of specific methods to cure malignant tumors, early screening and detection of malignant tumors can help improve the survival rate and cure rate of malignant tumor patients. Summary of the invention
[0007] The technical problem to be solved by the present invention is to provide a urine metabolic small molecule combination for early detection of lung cancer and its application, which can detect the functional status of the human body based on urine metabolites.
[0008] In order to solve the above technical problems, the technical solution provided by the present invention is: a urine metabolism small molecule combination, wherein the urine metabolism small molecule combination is 2,3-pinanediol.
[0009] Another aspect of the present invention provides an application of a urine metabolic small molecule combination in specific disease detection.
[0010] Another aspect of the present invention provides the use of 2,3-pinanediol as a biomarker in the early detection of lung cancer.
[0011] Preferably, the concentration of urine metabolic markers is detected based on chemical analysis or mass spectrometry.
[0012] The advantages of the present invention over the prior art are: concentration analysis is performed based on a small molecule combination of human urine metabolites, and the content of its biomarkers can be used as a biomarker for early detection of lung cancer, which is convenient for early detection of lung cancer, is beneficial for screening of high-risk groups, and realizes non-invasive diagnosis of tumors. BRIEF DESCRIPTION OF THE DRAWINGS
[0013] Figure 1 This is the TIC diagram of urine metabolites in normal female healthy volunteers.
[0014] Figure 2 This is the GC-MS analysis spectrum of urine metabolites from normal male healthy volunteers.
[0015] Figure 3 This is the GC-MS analysis spectrum of urine metabolites in male lung cancer patients.
[0016] Figure 4 This is the GC-MS analysis spectrum of urine metabolites in elderly male non-cancer smokers. DETAILED DESCRIPTION
[0017] The present invention is further described in detail below in conjunction with the accompanying drawings.
[0018] The present invention is specifically implemented:
[0019] A total of 49 urine samples were collected from adult males and females with relatively healthy physical examination results (cancer-free, normal urine pH range, urine white, red blood cell count and other test items) in tertiary hospitals, 34 urine samples from hospitalized patients (older smokers) who had been strictly tested in the respiratory department to exclude the possibility of cancer, and 13 morning urine midstream urine samples from male lung cancer patients (first diagnosed with lung cancer and not receiving drug treatment or chemotherapy). 10 ml of midstream urine was collected from the patient before breakfast.
[0020] 10 ml of midstream urine of lung cancer patients with fasting morning urine who met the inclusion criteria were collected from tertiary hospitals and placed in a sterile centrifuge tube, avoiding direct sunlight and placed in a foam box with ice packs to keep it at a low temperature. 5 ml of urine specimens retrieved from the hospital were taken and placed in another sterile centrifuge tube (urine samples frozen at -80 ° C need to be thawed before processing), and 5 ml of methanol (analytical grade) was taken and mixed evenly. Centrifuge at 3200 r / min (ordinary centrifuge) for 20 min and then 4 ml of supernatant was taken into a sterile EP tube. 1 ml of supernatant was taken with a 1 ml syringe and filtered through a 0.22 μm microporous membrane into a sample injection bottle for preparation of injection. (Normal human urine was treated in the same way as above) The simple process is as follows: fresh urine sample is retrieved → urine sample + methanol (methanol: urine sample = 1:1), mixed evenly → centrifuge (3200 r / min, 20 min) → take the supernatant and filter through a 0.22 μm microporous membrane into a sample injection bottle. Chromatographic conditions of gas chromatography-mass spectrometry (GC-MS): TG-WAXMS capillary column (30m×0.32mm×0.50μm), temperature program: 50℃ for 2min, 10℃ / min to 140℃, 5min, 10℃ / min to 200℃, 20min. Inlet temperature: 200℃ FID detector temperature: 200℃ carrier gas is nitrogen. Injection volume: 2μl split ratio is 1:3 (the content of the substance to be tested in the sample is low), full scan range (m / z): 50-650, other conditions are conventional.
[0021] Collect midstream urine samples according to the inclusion criteria of different populations → pre-treat the collected morning urine within two hours (freeze the collected morning urine in a -80°C ultra-low temperature refrigerator if it is not processed in time) → conduct preliminary experiments using the GC method to determine the chromatographic conditions, and count the specific peak substances by GC detection → filter the pre-treated urine and send it to GC-MS detection → GC-MS injection detection, compare the obtained GC-MS spectrum results with the mass spectrum database, perform fingerprint analysis, and qualitatively identify the specific substances → screen tumor markers after statistical analysis. Record the total ions chromatogram (TIC) of each urine sample obtained in the experiment. Compare the TIC with the National Institute of Standards Technology (NIST) 11.0 mass spectrum database, analyze the TIC and retrieve the corresponding compounds in the NIST 11.0 database, select the compounds with a matching degree higher than 70%, and calculate the detection rate.
[0022] result:
[0023] GC-MS analysis of urine metabolites of normal female volunteers, see Figure 1GC-MS analysis of urine metabolites of normal male volunteers, see Figure 2 GC-MS analysis of urine metabolites in male lung cancer patients, see Figure 3 GC-MS analysis of urine metabolites in elderly male non-cancer smokers, see Figure 4 .
[0024] Table 1 List of retention time, name, matching degree and detection rate of compounds with high detection rate in urine of lung cancer patients:
[0025]
[0026] The experimental results showed that a total of 49 healthy men and women were found to have one urinary small molecule metabolite with a high matching degree and detection rate, namely: Bicyclo(3.1.1)heptane-2,3-diol,2,6,6-trimethyl-(2,3-pinanediol).
[0027] Detection of Bicyclo(3.1.1)heptane-2,3-diol,2,6,6-trimethyl-(2,3-pinanediol) in lung cancer urine can develop biomarkers for early detection of lung cancer.
[0028] The contents not described in detail in this specification belong to the prior art known to professional and technical personnel in this field.
[0029] In addition, the terms "first" and "second" are used for descriptive purposes only and should not be understood as indicating or implying relative importance or implicitly indicating the number of the indicated technical features. Therefore, the features defined as "first" and "second" may explicitly or implicitly include one or more of the features. In the description of the present invention, the meaning of "plurality" is two or more, unless otherwise clearly and specifically defined.
[0030] In the present invention, unless otherwise clearly specified and limited, the terms "installed", "connected", "connected", "fixed" and the like should be understood in a broad sense, for example, it can be a fixed connection, a detachable connection, or an integral connection; it can be directly connected or indirectly connected through an intermediate medium, it can be the internal connection of two elements or the interaction relationship between two elements. For ordinary technicians in this field, the specific meanings of the above terms in the present invention can be understood according to specific circumstances.
[0031] In the present invention, unless otherwise clearly specified and limited, a first feature being "above" or "below" a second feature may include the first and second features being in direct contact, or may include the first and second features not being in direct contact but being in contact through another feature between them. Moreover, a first feature being "above", "above" and "above" a second feature includes the first feature being directly above and obliquely above the second feature, or simply means that the first feature is higher in level than the second feature. A first feature being "below", "below" and "below" a second feature includes the first feature being directly below and obliquely below the second feature, or simply means that the first feature is lower in level than the second feature.
[0032] The present invention and its embodiments are described above, and such description is not restrictive. The drawings show only one embodiment of the present invention, and the actual structure is not limited thereto. In short, if ordinary technicians in the field are inspired by it, without departing from the purpose of the invention, they can design a structure and embodiment similar to the technical solution without creativity, which should belong to the protection scope of the present invention.
Claims
1. A urine metabolism small molecule combination, characterized in that: The urine metabolite small molecule combination is 2,3-pinanediol.
2. Use of a urine metabolic small molecule combination according to claim 1 in specific disease detection.
3. The use of a urine metabolic small molecule combination in specific disease detection according to claim 2, characterized in that: The application of 2,3-pinanediol as a biomarker in the early detection of lung cancer.
4. The use according to claim 3, characterized in that: The concentration of urine metabolic markers is measured based on chemical analysis or mass spectrometry.