Plasma metabolic small molecule markers related to human non-small cell lung cancer and their application

A technology for non-small cell lung cancer and metabolic small molecules, which is applied in the fields of analytical chemistry and clinical medicine, can solve problems such as complex experimental steps, low sensitivity, and narrow detection dynamic range, so as to improve sensitivity and specificity, facilitate detection, and avoid Effect of Invasive Diagnostics

Inactive Publication Date: 2017-06-20
JIANGSU PROVINCE HOSPITAL
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

NMR is characterized by no damage to the components to be measured, simple sample pretreatment, but low sensitivity and narrow detection dynamic range; GC-MS has good sensitivity and reproducibility, but derivatization methods are generally used for sample pretreatment , making the experimental steps more complicated

Method used

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  • Plasma metabolic small molecule markers related to human non-small cell lung cancer and their application
  • Plasma metabolic small molecule markers related to human non-small cell lung cancer and their application
  • Plasma metabolic small molecule markers related to human non-small cell lung cancer and their application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0074] Example 1 Research Object Selection and Grouping Basis

[0075] From October 2011 to June 2014, the inventor collected blood samples from non-small cell lung cancer patients and healthy controls who met the requirements from the First Affiliated Hospital of Nanjing Medical University. 112 healthy controls (mean age: 58.5 years, range 42-80 years) and 99 patients with non-small cell lung cancer (mean age: 59.5 years, range 42-83 years) as non-small cell lung cancer metabolic small molecule biomarkers Objects for screening experiments. Specific sample classification criteria are as follows:

[0076] Group A: healthy control group (n=112, 56 people screened, 56 people verified by independent population):

[0077] 1. Aged between 42 and 80 years old;

[0078] 2. No tumor was diagnosed by physical examination, and no previous history of cancer;

[0079] 3. No other major systemic diseases;

[0080] 4. No chronic disease history of long-term medication.

[0081] Group B...

Embodiment 2

[0086] Example 2 The main diagnostic basis of the research object

[0087]The study was aimed at patients who were first diagnosed with non-small cell lung cancer by biopsy, cytology, and patients who had not undergone surgery, radiotherapy, or chemotherapy. The main diagnostic basis is: (1) Chest CT imaging findings: see figure 2 ; (2) results of puncture, biopsy, and cytopathological examination: see figure 1 .

[0088] The above clinical examination methods all have their limitations, among which chest CT diagnosis of lung cancer has high false negative and false positive results, and radiological methods have certain radiation damage to lung cancer patients. Puncture, biopsy, and cytology methods are more accurate, but they are invasive diagnostic methods, and the patient is already in the middle and late stages at the time of diagnosis, so the disease cannot be detected early. In clinical work, more patients are confirmed by pathological examination of surgical resect...

Embodiment 3

[0089] Example 3 UPLC-MS metabolomics non-small cell lung cancer biomarker screening

[0090] 1. Sample pretreatment

[0091] 1. Centrifuge the fresh blood at 3000rpm for 5min in a centrifuge, take 400μl of the supernatant and dispense it into clean 1.5ml EP tubes.

[0092] 2. Precipitate protein with 1200μl methanol in 400μl plasma.

[0093] 3. Aspirate the supernatant, divide it into 2 parts evenly, blow dry with nitrogen and then vacuum dry.

[0094] 4. Dissolve one part of the dry matter (acidic extract) in 50 μL of water (containing 0.1% formic acid), and dissolve the other part in 50 μL of water containing 6.5 mM ammonium bicarbonate pH=8 (basic extract).

[0095] 2. Instrument testing

[0096] 2.1 Analytical instrument: UPLC series ThermoFisher LTQ-FT linear ion trap cyclotron resonance mass spectrometer from Waters Acquity Company was used.

[0097] 2.2 Liquid phase conditions:

[0098] 2.2.1 The liquid chromatography column is Waters BEH C18 1.7μm 100mm column, a...

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Abstract

The invention belongs to the field of analytical chemistry and clinical medicine and relates to a plasma metabolization micromolecule marker related to the human non-small-cell lung cancer and an application of the plasma metabolization micromolecule marker. The plasma metabolization micromolecule marker related to the human non-small-cell lung cancer is one or more of cortisol, corticosterone and 4-methoxyphenylacetic acid. The plasma metabolization micromolecule marker is prepared from cortisol, corticosterone and 4-methoxyphenylacetic acid. The content range (95% confidence interval) of cortisol is 0.00018-0.00067, the content range (95% confidence interval) of corticosterone is 0.000029-0.00010, the content range (95% confidence interval) of 4-methoxyphenylacetic acid is 0.000015-0.000022, and metabolite can prompt occurrence of tumors within the ranges. The horizontal range, corresponding to a normal group, of cortisol is 0.0030-0.0037, the horizontal range, corresponding to the normal group, of corticosterone is 0.00044-0.00056, and the horizontal range, corresponding to the normal group, of 4-methoxyphenylacetic acid is 7.39 E-07-2.09 E-06. The plasma metabolization micromolecule marker is a novel biomarker, compared with a traditional protein biomarker, the relevance between the marker and the disease outcome is higher, and the plasma metabolization micromolecule marker is stable, minimally invasive, easy to detect and accurate in quantitation.

Description

[0001] field of invention [0002] The invention belongs to the field of analytical chemistry and clinical medicine, and relates to plasma metabolic small molecule markers related to human non-small cell lung cancer and applications thereof. Background technique [0003] Lung cancer is the most common cause of cancer-related death in both men and women worldwide. It is estimated that in 2012, there were 18 million new cases of lung cancer in the world, accounting for 12.9% of all new cancer cases, and 16 million deaths, accounting for 19.4% of all cancer-related deaths. Lung cancer is divided into non-small cell lung cancer and small cell lung cancer (15%) according to cell type. There are two main subtypes of non-small cell lung cancer: adenocarcinoma (40%) and squamous cell carcinoma (30%), depending on the type The treatment and prognosis also vary. [0004] At present, the imaging examination methods clinically used to diagnose lung cancer include: chest X-ray, CT (compu...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): G01N30/88
Inventor 郭人花向程程冯静夏彦恺金时代束永前
Owner JIANGSU PROVINCE HOSPITAL
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