CN110763795B - Serum biomarker for early diagnosis of schistosomiasis japonica, screening method and application - Google Patents

Serum biomarker for early diagnosis of schistosomiasis japonica, screening method and application Download PDF

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CN110763795B
CN110763795B CN201910272793.5A CN201910272793A CN110763795B CN 110763795 B CN110763795 B CN 110763795B CN 201910272793 A CN201910272793 A CN 201910272793A CN 110763795 B CN110763795 B CN 110763795B
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schistosomiasis japonica
early diagnosis
serum
schistosomiasis
japonica
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CN110763795A (en
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吕志跃
胡玥
陈剑松
黄萍
周洪利
马玉斌
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Sun Yat Sen University
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    • G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N30/02—Column chromatography
    • G01N30/04—Preparation or injection of sample to be analysed
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Abstract

The invention discloses a serum biomarker for early diagnosis of schistosomiasis japonica, wherein the serum biomarker is phosphatidylcholine and/or palmityl choline. The sensitivity and specificity of the marker are both greater than 0.9, and the area under the curve (AUC) is both greater than 0.9, which indicates that the two indexes are good in predictability and can be used for early diagnosis of schistosomiasis japonica. The invention also discloses a screening method of the schistosomiasis japonica early diagnosis serum biomarker based on metabonomics, which comprises the steps of constructing a mouse schistosomiasis japonica model, carrying out metabonomic analysis on mouse serum by using an ultra performance liquid chromatography-tandem mass spectrometry technology, and finding and analyzing characteristic difference metabolites between a normal mouse and a schistosomiasis japonica infected mouse, namely the schistosomiasis japonica early diagnosis biomarker. The screening method has the characteristics of convenience and quickness, can accurately reflect the metabolic spectrum difference between the schistosomiasis japonica infected mouse and the normal mouse, and has high specificity.

Description

Serum biomarker for early diagnosis of schistosomiasis japonica, screening method and application
Technical Field
The invention relates to the technical field of biomedicine, and more particularly relates to a serum biomarker for early diagnosis of schistosomiasis japonica, a screening method and application thereof.
Background
Schistosomiasis japonica, a zoonosis parasitic disease that seriously harms human health and hinders socioeconomic development, is caused by Schistosoma japonicum (Schistosoma japonicum), is widely prevalent in asia, and particularly in china, philippines and indonesia, more than 100 million people are infected with the schistosomiasis japonica, and about 4600 million people are threatened. In China, schistosoma japonicum is mainly popular in the middle and lower reaches of Yangtze river and 12 provinces, cities and autonomous regions in the south of the Yangtze river. After more than 60 years of efforts, the prevention and treatment work of schistosomiasis in China has achieved remarkable results, and the current popular areas are mainly distributed in 4 provinces of Anhui, Hubei, Hunan and Jiangxi, but the task is still arduous to achieve the goal of eliminating schistosomiasis nationwide.
The life history of schistosoma japonicum includes sexual reproduction in the terminal host body of human and several mammals and asexual reproduction in the only intermediate host body of oncomelania, and its development stage is divided into seven: eggs, hair larvae, mother larvae, daughter larvae, cercaria, baby larvae and adults. In the schistosoma japonicum infection stage, cercaria, schistosomulum, adult and ovum all can cause damage to a host, and the main reason of the damage is that antigens released during parasitism induce the immune response of the host, so that a series of complex immunopathological reactions occur, and the main reason of death of the disease is the ovum-induced liver granuloma and the subsequent hepatic fibrosis.
The diagnosis of schistosomiasis japonica at present mainly comprises a direct detection method and an indirect detection method. The former is mainly the etiology examination, namely the examination of the eggs in the excrement under a microscope; the latter includes immunological detection and molecular biological detection, such as detection of antigen or antibody in serum, detection of DNA of Schistosoma japonicum in feces, etc. In addition, imaging methods such as ultrasonic examination (US), Computed Tomography (CT), and Magnetic Resonance Imaging (MRI) can also be used for diagnosis of schistosomiasis japonica. However, the above diagnostic methods are low in either specificity or sensitivity and are not suitable for early diagnosis; therefore, there is a need to find a method for early diagnosis of schistosomiasis japonica.
Metabolomics (metabolomics) is a systematic biology subject developed after genomics and proteomics and related to the types, the quantities and the change rules of small molecular metabolites (molecular weight <1200Da) of a biological system after the biological system is stimulated or disturbed, and the corresponding relation between the metabolites and physiological and pathological changes is searched by analyzing the whole metabolic spectrum of an organism, so that a basis is provided for disease diagnosis and biomarkers (Biomarker) related to diseases are searched. The metabonomics analysis means mainly comprise Nuclear Magnetic Resonance (NMR), gas chromatography-mass spectrometry (GS/MS) coupling technology, liquid chromatography-mass spectrometry (LC/MS) coupling technology and the like, wherein ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-Q-TOF/MS) technology is taken as an advanced separation analysis technology and is widely applied to the research in the metabonomics field, and the strong analysis capability is known to be one of the best analysis technologies of complex samples. At present, the markers for early diagnosis of schistosomiasis japonica are not abundant enough, and the search for new diagnostic markers as far as possible is helpful for the development of early diagnosis of schistosomiasis japonica.
Disclosure of Invention
The invention aims to overcome the defects in the prior art and provide a serum biomarker for early diagnosis of schistosomiasis japonica.
The invention also aims to provide a screening method of the serum biomarker for early diagnosis of schistosomiasis japonica based on metabonomics.
The invention also aims to provide the application of the serum biomarker for early diagnosis of schistosomiasis japonica.
The above object of the present invention is achieved by the following technical solutions:
a serum biomarker for early diagnosis of schistosomiasis japonica, wherein the serum biomarker is phosphatidylcholine and/or palmityl choline.
The characteristic differential metabolite between a normal mouse and a schistosoma japonicum infected mouse is researched and analyzed based on metabonomics, and the schistosoma japonicum early diagnosis serum biomarker-phosphatidylcholine and/or phosphorus palmate based on the metabonomics is finally obtained, wherein the sensitivity and the specificity of the marker are both greater than 0.9, and the area under the curve (AUC) is both greater than 0.9, so that the two indexes are relatively good in predictability and can be used for the early diagnosis of schistosomiasis japonicum.
The application of phosphatidylcholine and/or palmityl choline as serum biomarker for early diagnosis of schistosomiasis japonica.
The invention also requests to protect the application of the serum biomarker in the preparation of schistosomiasis japonica early diagnosis products; the application of the serum biomarker in preparing and screening schistosomiasis japonica drugs.
An early diagnosis product for schistosomiasis japonica, which is used for judging whether a subject suffers from schistosomiasis japonica by detecting the concentration change of phosphatidylcholine and/or palmityl choline marker in the serum of the subject.
An early diagnosis product for schistosomiasis japonica contains a reagent for detecting the content concentration of phosphatidylcholine and/or palmityl choline marker in the serum of a subject.
The invention also provides a screening method of the schistosomiasis japonica early diagnosis serum biomarker based on metabonomics, which constructs a mouse schistosomiasis japonica model, utilizes an ultra performance liquid chromatography-tandem mass spectrometry technology to carry out metabonomic analysis on mouse serum, finds and analyzes characteristic difference metabolites between a normal mouse and a schistosomiasis japonica infected mouse, and the metabolite is the schistosomiasis japonica early diagnosis biomarker.
As a preferred embodiment, the screening method of the serum biomarker for early diagnosis of schistosomiasis japonica based on metabonomics specifically comprises the following steps:
(1) healthy mice were divided into seven experimental groups: normal control group, group for 3 days of Schistosoma japonicum infection, group for 7 days of Schistosoma japonicum infection, group for 14 days of Schistosoma japonicum infection, group for 21 days of Schistosoma japonicum infection, group for 28 days of Schistosoma japonicum infection and group for 42 days of Schistosoma japonicum infection; the normal control group is not treated, and the mice in the infected group are attached with a coverslip stained with cercaria to infect the schistosoma japonicum through the abdominal skin;
(2) collecting serum samples of seven experimental mice respectively, adding 90 μ L methanol into 10 μ L serum samples, mixing uniformly by vortex, precipitating protein at 4 deg.C overnight, centrifuging at 4 deg.C for 10min at 10000g, and collecting supernatant to obtain test solution;
(3) detecting the test solution by using ultra-high performance liquid chromatography-tandem mass spectrometry to obtain the fingerprint of the serum samples of the mice in the seven experimental groups;
(4) and finally obtaining the schistosomiasis japonica early diagnosis serum biomarker based on metabonomics by preprocessing data, performing multivariate statistical analysis and screening differential metabolites, and comparing the accurate molecular weights of the differential metabolites with a network database.
Preferably, the conditions of the liquid chromatography in the ultra performance liquid chromatography-tandem mass spectrometry are as follows: a chromatographic column: waters ACQUITY UPLC C18BEH column (2.1X 100mm, 1.7 μm); liquid chromatography conditions: mobile phase: A-H2O (0.1% formic acid), B-70% isopropanol + 30% acetonitrile (0.1% formic acid); flow rate: 0.4mL/min, column temperature: 38 ℃, sample introduction: 1.000 μ L; gradient elution procedure: 1% of B in 0-3 min, 40-85% of B in 3-18 min, 99% of B in 18-22 min and 1% of B in 22.1-25 min. (ii) a
Mass spectrum conditions: nitrogen is used as desolventizing agent and taper hole gas; capillary voltage of 2.5kV, ESI electrospray ion source, detection modes of MS and MSEThe taper hole voltage is 35kV, the reverse taper hole airflow is 30L/h, the ion source temperature is 110 ℃, the desolvation gas temperature is 350 ℃, and the desolvation gas flow is 700L/h; under the condition that the collision energy is 20-50 eV, the ion scanning time is 0.3s, and the data acquisition range is 50-1200 m/z. The leucine-enkephalin solution, ESI-554.2615m/z, was used for accurate mass determination.
Compared with the prior art, the invention has the following beneficial effects:
(1) the invention provides a serum biomarker for early diagnosis of schistosomiasis japonica, wherein the serum biomarker is phosphatidylcholine and/or palmityl choline, the sensitivity and specificity of the marker are both greater than 0.9, and the area under the curve (AUC) is both greater than 0.9, which indicates that the two indexes are good in predictability and can be used for early diagnosis of schistosomiasis japonica.
(2) The invention carries out metabonomics analysis on mouse serum by an ultra-high performance liquid chromatography-tandem mass spectrometry technology, and carries out model construction and discriminant analysis on response intensity data of substance peaks in all samples, thereby finding out characteristic differential metabolites between a normal mouse and a schistosoma japonicum infected mouse, further analyzing content change of the characteristic differential metabolites, and finding out specific differential metabolites caused by schistosomiasis japonica, namely early diagnosis molecular markers of schistosomiasis japonica. The method provided by the invention has the characteristics of convenience and rapidness, can accurately reflect the metabolic spectrum difference between the schistosomiasis japonica infected mouse and the normal mouse, and has high specificity.
Drawings
Fig. 1 is a Base Peak Intensity (BPI) chromatogram of seven experimental groups in positive ion mode.
Fig. 2 is a Base Peak Intensity (BPI) chromatogram for seven experimental groups in negative ion mode.
FIG. 3 is a graph of the scores of PCA and PLS-DA in the positive and negative ion mode for seven experimental groups; (A) PCA score plot in positive ion mode; (B) PCA score plot in negative ion mode; (C) PLS-DA score plot in positive ion mode; (D) PLS-DA score plot in negative ion mode.
FIG. 4 is a plot of OPLS-DA scores and S-plot for seven experimental groups in positive ion mode.
FIG. 5 is the OPLS-DA score plot and S-plot for seven experimental groups in negative ion mode.
Fig. 6 is the abundance of two serum biomarkers in seven experimental groups (a) and the corresponding ROC curves (B).
Detailed Description
The invention is further described with reference to the drawings and the following detailed description, which are not intended to limit the invention in any way. Reagents, methods and apparatus used in the present invention are conventional in the art unless otherwise indicated.
Unless otherwise indicated, reagents and materials used in the following examples are commercially available.
Example 1
1. Japanese blood fluke infected mouse model establishment
Healthy SPF grade 8 week old BALB/c mice were divided into seven groups: normal control group, group of 3 days of Schistosoma japonicum infection, group of 7 days of Schistosoma japonicum infection, group of 14 days of Schistosoma japonicum infection, group of 21 days of Schistosoma japonicum infection, group of 28 days of Schistosoma japonicum infection and group of 42 days of Schistosoma japonicum infection, each group comprises 10 mice. The normal control group was not treated, and the mice in the infected group were infected according to the conventional method: placing the positive oncomelania in dechlorinated water, releasing cercaria for 1-2h under the illumination condition of 25-28 ℃, dipping 30 cercarias on the water surface by using an inoculating ring, and collecting the cercarias on a cover glass. After anaesthetizing, the mice were fixed on a rat plate with the abdomen facing upwards, the abdomen was shaved and then moistened with dechlorinated water, and the coverslip with cercaria was attached to the skin of the abdomen of the mice for 20min for infection.
2. Sample collection and pretreatment
The mice of each experimental group are respectively anesthetized, cervical vertebra dislocation is killed, blood is taken from fundus venous plexus, after serum is solidified, 3000g is centrifuged for 10min, and supernatant is collected to be a serum sample, and the serum sample is subpackaged and frozen at minus 80 ℃. Before the serum sample is analyzed by adopting the ultra performance liquid chromatography-tandem mass spectrometry, 10 mu L of the serum sample is unfrozen at 4 ℃, 90 mu L of methanol is added, protein is precipitated at 4 ℃ overnight after vortex mixing, then 10000g of the mixture is centrifuged for 10min, and about 80 mu L of supernatant is taken and added into an inner lining pipe for metabonomics analysis.
3. Metabonomic analysis was performed based on the 70 samples described above, with the following specific analysis conditions:
(1) instrumentation and equipment
Liquid chromatography: waters ACQUITY UPLC-I Class System
Mass spectrum: waters SYNAPT G2-Si HDMS
A chromatographic column: waters ACQUITY UPLC C18BEH column (2.1X 100mm, 1.7 μm)
(2) Conditions of liquid chromatography
Mobile phase: A-H2O (0.1% formic acid), B-70% isopropanol + 30% acetonitrile (0.1% formic acid)
Flow rate: 0.4mL/min, column temperature: 38 ℃, sample introduction: 1.000 μ L
Gradient elution procedure: 1% of B in 0-3 min, 40-85% of B in 3-18 min, 99% of B in 18-22 min and 1% of B in 22.1-25 min.
(3) Conditions of Mass Spectrometry
Nitrogen gas is used as desolventizing agent and taper hole gas. Capillary voltage of 2.5kV, ESI electrospray ion source, detection modes of MS and MSEThe cone hole voltage is 35kV, the reverse cone hole airflow is 30L/h, the ion source temperature is 110 ℃, the desolvation gas temperature is 350 ℃, and the desolvation gas flow is 700L/h. Ion scanning time under the condition that the collision energy is 20-50 eVThe time is 0.3s, and the data acquisition range is 50-1200 m/z. Accurate mass determination leucine-enkephalin solution, ESI-554.2615m/z, was used to ensure mass accuracy and reproducibility.
4. Data analysis
(1) Data pre-processing
Raw data are collected by using Masslynx software, and the obtained raw data are introduced into Progenetics QI to be subjected to noise removal, mass spectrum peak extraction, peak arrangement, peak alignment, normalization and other processing, so that a Base Peak Intensity (BPI) chromatogram under a positive ion mode and a negative ion mode of each group of samples is obtained, as shown in figures 1 and 2.
(2) Multivariate statistical analysis
Multivariate statistical analysis was performed using SIMCA-P and MetabioAnalyst, and to investigate the metabolic changes in each infected group compared to the control group, the differences were characterized using unsupervised Principal Component Analysis (PCA) and supervised partial least squares discriminant analysis (PLS-DA), R2The value is the model's interpretation rate, Q2The values are the prediction rates of the models, see FIG. 3.
As can be seen from the PCA and PLS-DA score maps of the normal control group and each infection group, the normal control group and each infection group have a certain separation tendency, and the fitting degree and the prediction capability of PLS-DA are good.
(3) Discovery and analysis of characteristic differential metabolites
Differential metabolites were further screened using orthogonal partial least squares discriminant analysis (OPLS-DA) and statistical analysis of the differential variables between groups was performed by one-way ANOVA, with p <0.05 indicating that the differences were statistically significant. Differential metabolites were considered when the variable importance in the projection (VIP) >2, p <0.05 and the minimum Coefficient of Variation (CV) ≧ 30, see FIGS. 4 and 5.
The exact molecular weights and retention times of the differential metabolites of the normal control and schistosoma japonicum 3 day infected groups were compared to the human metabolome database (HMDB, http:// www.hmdb.ca) and the METLIN database (http:// METLIN. script. edu) and the identified substances were used as potential biomarkers (see Table 1).
TABLE 1 serum characteristic differential metabolites between normal mice and Schistosoma japonicum infected mice
Figure BDA0002018959210000061
Finally, the diagnostic ability of the biomarkers was assessed using receiver operating characteristic curve (ROC curve) analysis. The sensitivity and specificity of phosphatidylcholine and palmityl choline were both greater than 0.9, and the area under the curve (AUC) was both greater than 0.9, suggesting that these two indices are more predictive, as shown in fig. 6.

Claims (3)

1. Palm bilip is used as a serum biomarker for early diagnosis of schistosomiasis japonica in preparation of an early diagnosis product of schistosomiasis japonica.
2. An early diagnosis product for schistosomiasis japonica is characterized in that whether a subject suffers from schistosomiasis japonica is judged by detecting the concentration change of a palm cholesterol marker in serum of the subject.
3. An early diagnosis product for schistosomiasis japonica, which is characterized by comprising a reagent for detecting the content concentration of palm cholesterol marker in serum of a subject.
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CN113341009B (en) * 2021-05-25 2023-09-08 海南医学院 Early diagnosis urine biomarker for Guangzhou pipe-line nematode disease and application thereof
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Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101565705A (en) * 2008-04-22 2009-10-28 中国疾病预防控制中心寄生虫病预防控制所 Schistosoma japonicum microsatellite locus and application thereof
WO2016036902A1 (en) * 2014-09-03 2016-03-10 Moderna Therapeutics, Inc. Tolerogenic compositions and methods
CN108707655A (en) * 2018-05-11 2018-10-26 中山大学 The application of serodiagnosis marker occurs as Japanese schistosomiasis liver fibrosis for β-actin albumen

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8784881B2 (en) * 2004-03-05 2014-07-22 Board Of Regents, The University Of Texas System Liposomal curcumin for treatment of diseases

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101565705A (en) * 2008-04-22 2009-10-28 中国疾病预防控制中心寄生虫病预防控制所 Schistosoma japonicum microsatellite locus and application thereof
WO2016036902A1 (en) * 2014-09-03 2016-03-10 Moderna Therapeutics, Inc. Tolerogenic compositions and methods
CN108707655A (en) * 2018-05-11 2018-10-26 中山大学 The application of serodiagnosis marker occurs as Japanese schistosomiasis liver fibrosis for β-actin albumen

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
Metabolite profiling for biomarkers in Schistosoma haematobium infection and associated bladder pathologies;Adewale S. Adebayo et al;《PLoS Negl Trop Dis》;20180430;第12卷(第4期);1-17 *
Quantitative analysis of phosphatidylcholine molecular species using HPLC and light scattering detection;Jos F. H. M. Brouwers et al;《Journal of Lipid Research》;19981231;第39卷;344-353 *

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