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CN-122017244-A - Plasma metabolism marker for kidney cancer diagnosis and application thereof

CN122017244ACN 122017244 ACN122017244 ACN 122017244ACN-122017244-A

Abstract

The application belongs to the technical field of biomedicine, and particularly relates to a plasma metabolism marker for diagnosing renal cancer and application thereof. The application provides a group of brand-new plasma metabolism marker combinations, which can synergistically and accurately distinguish healthy people from patients with early and late renal cancers, provide novel and reliable biomarkers for molecular diagnosis of renal cancers, and can effectively distinguish healthy people from patients with early and late renal cancers by detecting the cooperative change of 13 metabolites in plasma. Among them, the occurrence and development of kidney cancer is accompanied by deep reprogramming of the metabolic network of the organism, these metabolites involve a number of key pathways of amino acid metabolism, sugar metabolism and lipid metabolism, and the change in abundance thereof can sensitively reflect the proliferation state, invasiveness and systemic response of the organism to the tumor from the molecular level.

Inventors

  • LI YAN
  • Hu Juanyuan
  • WEN HE
  • MA SHUANG
  • YU SHUQI
  • WANG ZHIPENG
  • LI MEIYI
  • LIANG JIELING
  • PENG XING
  • Che Sijia

Assignees

  • 哈尔滨脉图精准技术有限公司

Dates

Publication Date
20260512
Application Date
20251210

Claims (10)

  1. 1. Application of detection reagent of kidney cancer diagnosis biomarker in preparing kidney cancer diagnosis kit; The kidney cancer diagnosis biomarker comprises L-valyl-L-serine, mannose, L-glutamyl-L-serine, fucose, L-citrulline, beta-hydroxy pyruvic acid, aspartic acid, 5-hydroxy-L-tryptophan, 3-hydroxy propionic acid, 2-oxo-glutaric acid, 2-hydroxy valeric acid, lysophosphatidylcholine 18:0e and lysophosphatidylcholine 16:0e.
  2. 2. Application of detection reagent of kidney cancer diagnosis biomarker in preparing kidney cancer diagnosis kit; The kidney cancer diagnosis biomarker is one or more of L-valyl-L-serine, L-glutamyl-L-serine, fucose, L-citrulline, beta-hydroxy pyruvic acid, aspartic acid, 5-hydroxy-L-tryptophan, 3-hydroxy propionic acid, 2-oxo glutaric acid, lysophosphatidylcholine 18:0e and lysophosphatidylcholine 16:0 e.
  3. 3. Application of detection reagent of kidney cancer diagnosis biomarker in preparing kidney cancer diagnosis kit; the kidney cancer diagnosis biomarker is one or more of L-valyl-L-serine, L-glutamyl-L-serine, fucose, L-citrulline, beta-hydroxy pyruvic acid, aspartic acid, 3-hydroxy propionic acid, 2-oxo glutaric acid and lysophosphatidylcholine 18:0e.
  4. 4. Application of detection reagent of kidney cancer diagnosis biomarker in preparing kidney cancer diagnosis kit; The kidney cancer diagnosis biomarker is one or more of L-valyl-L-serine, L-glutamyl-L-serine, fucose, beta-hydroxy pyruvic acid, aspartic acid, 3-hydroxy propionic acid and lysophosphatidylcholine 18:0e.
  5. 5. The use according to any one of claims 1 to 4, wherein the sample to be detected by the detection reagent comprises a plasma sample.
  6. 6. The use according to any one of claims 1 to 4, wherein the detection reagent detects the renal cancer diagnostic biomarker by high performance liquid chromatography mass spectrometry.
  7. 7. The use according to claim 6, wherein, In the case where the sample detected by the detection reagent is prepared as an organic phase test liquid, the liquid chromatography condition satisfies one or more of the following conditions: (1) With the use of the C8 chromatographic column, (2) Mobile phase A is aqueous solution containing 0.08 v/v% -0.12 v/v% acetic acid and 10mmol/L-20mmol/L ammonium acetate, A mobile phase B, which is acetonitrile-isopropanol solution containing 0.08 v/v% -0.12 v/v% acetic acid and 10mmol/L-20mmol/L ammonium acetate, wherein the volume ratio of acetonitrile to isopropanol is (6-8): 2-4; (3) The elution mode comprises gradient elution, Optionally, the gradient elution procedure comprises: 0-12 minutes, wherein the volume ratio of the mobile phase B is increased from 55% to 89%; 12 minutes to 19.5 minutes, the volume ratio of the mobile phase B is increased from 89% to 100%; In the case where the sample detected by the detection reagent is prepared as an aqueous phase test solution, the liquid chromatography condition satisfies one or more of the following conditions: (1) By adopting the T3 chromatographic column, (2) Mobile phase A is aqueous solution containing 0.08 v/v% to 0.12/v/v% formic acid, Mobile phase B is acetonitrile solution containing 0.08 v/v% to 0.12/v/v% formic acid; (3) The elution mode comprises gradient elution, and optionally, the gradient elution program comprises: 0-13 minutes, wherein the volume ratio of the mobile phase B is increased from 1% to 70%; 13-18 minutes, the volume ratio of the mobile phase B is increased from 70% to 99%.
  8. 8. The use of claim 6, wherein the mass spectrometry conditions of the high performance liquid chromatography mass spectrometry meet one or more of the following conditions: (1) Collecting in a Full MS mode and a Full MS/dd-MS2 mode, wherein the Full MS mode and the Full MS/dd-MS2 mode comprise a positive mode and a negative mode; (2) Resolution is 3.5-7 ten thousand; (3) The scanning range is 100 m/z-1500 m/z; (4) The automatic gain control is 1.0×10 6 -3.0×10 6 ; (5) Maximumit is 180 ms-220 ms; (6) HCD has a relative collision energy of 20% -80%, and (7) The maximum ion implantation time is 40ms-60ms.
  9. 9. The use according to any one of claims 1 to 3 and 7 to 8, wherein the kit further comprises reagents for extracting the kidney cancer diagnostic biomarker from a sample; optionally, the reagent for extracting the kidney cancer diagnostic biomarker from the sample comprises one or both of methyl tert-butyl ether and methanol; alternatively, the volume ratio of the methyl tertiary butyl ether to the methanol is (2-4): 1.
  10. 10. A method of constructing a diagnostic model of renal cancer, comprising: Respectively detecting and identifying small molecular metabolites of plasma samples of a healthy population and a kidney cancer population in the building block to respectively obtain healthy population data and kidney cancer population data in the building block; Performing a significantly different metabolite analysis on the healthy population data and the kidney cancer population data of different stages in the building block, screening small molecule metabolites with significantly different groups to obtain a metabolic marker combination, and Multivariate ROC curve analysis was performed on the metabolic marker combinations.

Description

Plasma metabolism marker for kidney cancer diagnosis and application thereof Technical Field The application belongs to the technical field of biomedicine, and particularly relates to a plasma metabolism marker for diagnosing renal cancer and application thereof. Background Renal cancer is one of the most lethal malignant tumors of the urinary system, with a survival rate of about 75% in 5 years, but suddenly drops to 15% if metastasis occurs. At present, more than 60% of patients with renal cancer are still diagnosed when they have typical symptoms such as hematuria and lumbago, and the patients have advanced stages and lose the opportunity of radical cure. Because of the lack of a high-sensitivity means capable of early detection of asymptomatic small kidney cancer (less than or equal to 4 cm), a minimally invasive, repeatable and cost-controllable molecular diagnosis tool is needed clinically to realize early screening and accurate staging of kidney cancer, so that the defects of insufficient identification of micro-metastasis and sampling deviation of puncture biopsy in imaging (CT/MRI) are overcome. The treatment strategies of the kidney cancer under different stages are obviously different, the limited (stage I-II) patients are preferably subjected to partial or radical resection, the disease-free survival rate of 5 years after operation can be more than 80%, the local advanced stage (stage III) needs to be combined with lymph node cleaning and perioperative targeting/immunotherapy to reduce the recurrence risk, the metastatic (stage IV) patients are mainly treated by a system, and comprise tyrosine kinase inhibitors, immune checkpoint inhibitors and emerging double immune combined schemes, and the operation is only used for tumor reduction or palliative purposes. Therefore, accurately distinguishing between phases I-II and III-IV within a "curable window" is critical to avoid over-treatment or delay systemic treatment, increasing overall survival. Currently, clinical staging of renal cancer is mainly dependent on imaging techniques such as Computed Tomography (CT) and Magnetic Resonance Imaging (MRI). However, these prior arts have limitations in that, firstly, the imaging method has limited sensitivity to tiny metastatic lesions (especially lesions smaller than 1cm in diameter) possibly resulting in underestimation of stage and missing of optimal treatment timing, secondly, the imaging examination result mainly reflects morphological characteristics of tumor, it is difficult to provide direct information about biological behaviors such as malignancy degree and proliferation activity of tumor, and the requirement of accurate stage cannot be fully satisfied, and furthermore, the imaging examination has disadvantages of radiation exposure, high cost and the like, and is not suitable for frequent disease monitoring. Therefore, it is of great clinical value to develop a diagnostic tool that accurately and noninvasively reflects the biological properties of renal cancer and effectively distinguishes between stages. Disclosure of Invention Based on this, an embodiment of the present application provides a plasma metabolic marker for renal cancer diagnosis and uses thereof. In one aspect, the application provides the use of a detection reagent for a kidney cancer diagnostic biomarker in the preparation of a kidney cancer diagnostic kit; The kidney cancer diagnosis biomarker comprises L-valyl-L-serine, mannose, L-glutamyl-L-serine, fucose, L-citrulline, beta-hydroxy pyruvic acid, aspartic acid, 5-hydroxy-L-tryptophan, 3-hydroxy propionic acid, 2-oxo-glutaric acid, 2-hydroxy valeric acid, lysophosphatidylcholine 18:0e and lysophosphatidylcholine 16:0e. In some of these embodiments, the renal cancer diagnostic biomarker is one or more of L-valyl-L-serine, L-glutamyl-L-serine, fucose, L-citrulline, β -hydroxypyruvate, aspartic acid, 5-hydroxy-L-tryptophan, 3-hydroxypropionic acid, 2-oxoglutarate, lysophosphatidylcholine 18:0e, and lysophosphatidylcholine 16:0 e. In some of these embodiments, the renal cancer diagnostic biomarker is one or more of L-valyl-L-serine, L-glutamyl-L-serine, fucose, L-citrulline, β -hydroxypyruvate, aspartic acid, 3-hydroxypropionic acid, 2-oxoglutarate, and lysophosphatidylcholine 18:0 e. In another aspect, the application provides the use of a detection reagent for a biomarker for diagnosing renal cancer in the preparation of a kit for diagnosing renal cancer; The kidney cancer diagnosis biomarker is one or more of L-valyl-L-serine, L-glutamyl-L-serine, fucose, beta-hydroxy pyruvic acid, aspartic acid, 3-hydroxy propionic acid and lysophosphatidylcholine 18:0e. In some of these embodiments, the sample detected by the detection reagent comprises a plasma sample. In some of these embodiments, the detection reagent detects the kidney cancer diagnostic biomarker by high performance liquid chromatography mass spectrometry. In some embodiments, the liquid chromatography uses the C8 chroma