Markers, products and systems for identification of hepatic echinococcosis

Abstract

The present invention belongs to the field of biomedical technology, and specifically relates to a marker, product and system for identifying hepatic echinococcosis. The present invention provides for the first time a marker for identifying hepatic echinococcosis, specifically a terminal galactose index of the biantennary complex N-sugar chain on the surface of blood immunoglobulin G. This indicator has high specificity, high sensitivity and high accuracy for the differential diagnosis of hepatic echinococcosis, and is of great clinical significance. The present invention relates to products based on the marker, including kits, equipment, operational systems and / or combinations thereof; including identification modules and systems based on the marker. The present invention helps to change the current status of the diagnosis of hepatic echinococcosis, and has important clinical value for the diagnosis and identification of hepatic echinococcosis.

Description

Technical Field

[0001] The present invention belongs to the field of biomedical technology, and in particular relates to hepatic echinococcosis identification markers, products and systems. Background Art

[0002] Echinococcosis (also known as echinococcosis) is a zoonotic parasitic disease. The most serious harm to the human body is caused by cystic echinococcosis (CE) and alveolar echinococcosis (AE) caused by Echinococcus granulosus and Echinococcus multilocularis. The liver is the organ with the highest incidence of echinococcosis. Patients have no clinical symptoms in the early stage. Most patients are only discovered during the screening of hepatic echinococcosis, which seriously affects the health of people in pastoral areas. When diagnosing alveolar hepatic echinococcosis with imaging, it is easy to be confused with liver cancer and misdiagnose.

[0003] Glycosylation is a post-translational modification (PTM) that is widely present in organisms and has an important influence on the chemical and biological properties of proteins. Serum immunoglobulin G (IgG) is a soluble serum glycoprotein, accounting for about 75% of the total immunoglobulin in peripheral blood. Both its Fc (crystallization segment) and Fab (antigen binding segment) can contain conservative N-glycosylation modifications. Depending on the glycosylation site and glycosylation form of immunoglobulin IgG, its immunological characteristics are significantly different. Some studies have reported that the level of galactosylated N-glycans of IgG in ovarian cancer, prostate cancer, gastric cancer and lung cancer has a downward trend. Therefore, IgG glycosylation modification is closely related to the occurrence and development of the disease. It is a potential biomarker with high clinical application value, which can be used to assist in the diagnosis and prognosis evaluation of related diseases.

[0004] Therefore, there is an urgent need in this field to develop a highly sensitive and specific identification marker for distinguishing hepatic echinococcosis from healthy controls and alveolar hepatic echinococcosis from liver cancer, so as to achieve the purpose of accurate diagnosis. Summary of the invention

[0005] The purpose of the present invention is to provide a marker for differential diagnosis of hepatic echinococcosis (cystic and alveolar types) with high specificity, high sensitivity and high accuracy, a blood IgG surface biantennary complex N-sugar chain terminal galactose index and a product for differentiating hepatic echinococcosis (cystic and alveolar types) from healthy controls and alveolar hepatic echinococcosis from liver cancer, so as to change the current status of differential diagnosis of hepatic echinococcosis.

[0006] The present invention first provides a marker for identifying hepatic echinococcosis (including cystic and alveolar types), specifically a biantennary complex N-sugar chain terminal galactose index on the surface of blood IgG, denoted as Gal, wherein Gal=G0 / (G1+2G2), G0 represents biantennary complex N-sugar chain HexNAc(4)Hex(3)Fuc(1), G1 represents biantennary complex N-sugar chain HexNAc(4)Hex(4)Fuc(1), G2 represents biantennary complex N-sugar chain HexNAc(4)Hex(5)Fuc(1), HexNAc represents N-acetylglucosamine (GlcNAc), Hex represents hexose (high mannose Man or galactose Gal), and Fuc represents fucose. The structure is shown in FIG. Figure 1 shown.

[0007] The present invention further provides a product for distinguishing hepatic echinococcosis (cystic and alveolar forms) and distinguishing alveolar hepatic echinococcosis from liver cancer. The product may be, for example, a kit, a device, an operating system and / or a combination thereof, and the product comprises:

[0008] (A) A reagent, instrument and / or system for determining the terminal galactosylation of biantennary complex N-glycan chains on the surface of blood immunoglobulin G, which is used to determine biantennary complex N-glycan chains G0 with no galactose linkage at the terminal of IgG surface, biantennary complex N-glycan chains G1 with one galactose linkage at the terminal, and biantennary complex N-glycan chains G2 with two galactose linkages at the terminal;

[0009] For example, reagents, instruments and / or systems for one or more methods selected from the group consisting of: matrix-assisted laser desorption time-of-flight mass spectrometry (MALDI-MS), fast atom bombardment mass spectrometry (FAB-MS), electrospray mass spectrometry (ES-MS); liquid chromatography; ultra-high performance liquid chromatography; liquid chromatography-mass spectrometry, sugar chip technology; microfluidics; enzyme-linked immunosorbent assay; liquid chip technology; nuclear magnetic resonance NMR, preferably ultra-high performance liquid chromatography;

[0010] (B) a module and / or processor for calculating Gal;

[0011] (C) Optional modules and / or processors for Gal-based differentiation of patients with hepatic echinococcosis (cystic and alveolar) from healthy controls and patients with alveolar hepatic echinococcosis from patients with liver cancer.

[0012] In some embodiments, the product further comprises one or more selected from the group consisting of:

[0013] (a) Reagents and / or instruments for collecting and / or processing blood samples from subjects;

[0014] (b) reagents and / or instruments for collecting and / or purifying serum and / or plasma samples from subjects;

[0015] (c) Reagents and / or instruments for collecting and / or purifying serum and / or plasma IgG from subjects;

[0016] (d) Reagents and / or instruments for separating, purifying and / or enriching serum / plasma IgG surface N-glycans;

[0017] For example, the reagents and / or instruments for the method of separating and purifying N-sugar chains are selected from the following group: HILIC extraction method (preferably using water-activated zwitterionic hydrophilic interaction reverse phase chromatography column (ZIC-HILIC) filler, balancing the ZIC-HILIC filler with acetonitrile: water: trifluoroacetic acid = 80:19.9:0.1, and eluting the sugar chains with a mixed solvent of acetonitrile: water: trifluoroacetic acid = 10:89.95:0.05), porous graphitized carbon PGC fixed extraction method, polysaccharide purification column, lectin affinity method, capillary electrophoresis, high performance liquid chromatography;

[0018] (e) Reagents and / or instruments for labeling (e.g., fluorescent labeling) IgG surface N-glycans;

[0019] (f) a database, module and / or processor for storing and / or processing the ratio of the abundance of terminal degalactose of biantennary complex N-glycans to monolactose and dilactose chains in the blood of a subject as an indicator of the degree of IgG surface galactosylation;

[0020] (g) A module and / or processor for determining hepatic echinococcosis (cystic and alveolar types) and distinguishing patients with alveolar hepatic echinococcosis from patients with liver cancer based on blood immunoglobulin G galactosylation indicators;

[0021] (h) A module and / or processor for providing test results and / or reports.

[0022] The present invention also provides a module for identifying hepatic echinococcosis, comprising:

[0023] (i) Hepatic echinococcosis (cystic and alveolar) and healthy control identification submodule: When the blood IgG galactosylation index Gal is higher than a pre-set range (e.g., 5% to 50% or any point or sub-range within the range), it is determined that the subject is likely to have hepatic echinococcosis (cystic and alveolar);

[0024] (ii) A submodule for differential diagnosis of cystic hepatic echinococcosis and alveolar hepatic echinococcosis: when the blood IgG galactosylation index Gal is higher than the range of the serum IgG galactosylation index Gal for cystic hepatic echinococcosis (e.g., 5% to 50% or any point or subrange within the range), it is determined that the subject has the possibility of alveolar hepatic echinococcosis;

[0025] (iii) Submodule for differential diagnosis of alveolar hepatic echinococcosis and liver cancer: When the blood IgG galactosylation index Gal is higher than the pre-set range of serum IgG galactosylation index Gal for the liver cancer group (e.g., 5% to 50% or any point or sub-range within the range), it is determined that the subject is likely to have alveolar hepatic echinococcosis.

[0026] The identification module is implemented by a software system, including the calculation and identification of Gal.

[0027] In the present invention, the blood sample that can be collected is whole blood, serum and / or plasma separated and preserved by conventional methods, preferably serum; the subject is a mammal, preferably a human, monkey, dog, horse, cow, sheep, pig, mouse, rabbit, etc.

[0028] In the present invention, the marker and the detection method used include the following steps:

[0029] Separating and / or purifying serum or blood IgG from a subject's blood sample using an IgG affinity purification column, preferably using an equilibration buffer, a binding buffer, and an elution buffer that are compatible with the purification column;

[0030] Treat the N-glycan of IgG with a glycosidase, preferably PNGaseF;

[0031] N-glycans are purified using a zwitterionic hydrophilic interaction (ZIC-HILIC) filler, preferably using pure water to activate the ZIC-HILIC filler, balancing the ZIC-HILIC filler with acetonitrile: water: trifluoroacetic acid = 80:19.9:0.1, and eluting the glycans with a mixed solvent of acetonitrile: water: trifluoroacetic acid = 10:89.95:0.05.

[0032] In the present invention, the Gal calculation is performed using a formula selected from the following group: Gal ratio = G0 / (G1+2G2), or other transformation forms such as its reciprocal, logarithm, etc.

[0033] Based on the subject's serum or blood IgG galactosylation index Gal, it is determined whether the subject suffers from hepatic echinococcosis (cystic type and alveolar type) (including differential diagnosis of the two) and to distinguish patients with alveolar hepatic echinococcosis from patients with liver cancer.

[0034] The present invention also provides a system for identifying hepatic echinococcosis (including cystic and alveolar types), the system comprising:

[0035] (a) a blood sample collection module, used to collect and / or process a blood sample of a subject;

[0036] (b) a blood sample purification module, used for collecting and / or purifying serum and / or plasma samples of a subject;

[0037] (c) an IgG collection and / or purification module, used for collecting and / or purifying serum and / or plasma IgG from a subject;

[0038] (d) an IgG surface N-glycan separation and purification module, used for separating, purifying and / or enriching serum / plasma IgG surface N-glycans;

[0039] (e) a labeling module for labeling (e.g., fluorescent labeling) IgG surface N-glycans;

[0040] (f) a storage module for storing and / or processing the ratio of the abundance of biantennary complex N-glycans terminally degalactose to monolactose and dilactose chains in the blood of the subject as an indicator of the degree of galactosylation on the surface of IgG;

[0041] (g) Identification module, used to judge hepatic echinococcosis (cystic and alveolar types) and to differentiate patients with alveolar hepatic echinococcosis from liver cancer according to the blood immunoglobulin G galactosylation index; it includes: Gal calculation module and discrimination module; Gal calculation module is used to calculate the blood immunoglobulin G galactosylation index Gal; the discrimination module uses Gal to identify the hepatic echinococcosis status:

[0042] (1) Gal distinguishes hepatic echinococcosis (cystic and alveolar) groups from normal healthy groups:

[0043] Gal distinguishes the cystic hepatic echinococcosis group and the normal healthy group: if the serum IgG surface galactosylation index Gal in the cystic hepatic echinococcosis group is higher than the range of the normal healthy group (e.g. 5% to 50% or any point or sub-range within the range), it is determined that the subject has the possibility of cystic hepatic echinococcosis;

[0044] Gal distinguishes the alveolar hepatic echinococcosis group and the normal healthy group: if the serum IgG surface galactosylation index Gal in the alveolar hepatic echinococcosis group is higher than the range of the normal healthy group (e.g. 5% to 50% or any point or sub-range within the range), it is determined that the subject has the possibility of alveolar hepatic echinococcosis;

[0045] (2) Gal differentiation between cystic hepatic echinococcosis group and alveolar hepatic echinococcosis group: If the serum IgG surface galactosylation index Gal in the alveolar hepatic echinococcosis group is higher than the range of the cystic hepatic echinococcosis group (e.g., 5% to 50% or any point or sub-range within this range), it is determined that the subject is likely to have alveolar hepatic echinococcosis;

[0046] (3) Gal differentiation between the alveolar hepatic echinococcosis group and the liver cancer group: If the serum IgG surface galactosylation index Gal in the alveolar hepatic echinococcosis group is higher than the range of the liver cancer group (e.g., 5% to 50% or any point or sub-range within this range), it is determined that the subject is likely to have alveolar hepatic echinococcosis;

[0047] (h) A display module, used to display and provide test results and / or reports.

[0048] The present invention realizes the determination of serum or blood IgG galactosylation index Gal in hepatic echinococcosis (cystic and alveolar types) (including differential diagnosis of the two) and differentiation between patients with alveolar hepatic echinococcosis and patients with liver cancer, as well as any combination of the above-mentioned technical schemes, technical features and performances without departing from the concept and protection scope of the present invention.

[0049] The beneficial effects of the present invention are as follows: the present invention provides a serum or blood IgG galactosylation index Gal for the blood diagnosis of hepatic echinococcosis (cystic and alveolar types) (including the differential diagnosis of the two) and the differentiation of alveolar hepatic echinococcosis and liver cancer. This potential differential index can improve clinical diagnostic capabilities, help change the current status of diagnosis of hepatic echinococcosis, and has important clinical value for early detection and early treatment of hepatic echinococcosis.

[0050] Specifically, the present invention conducted the following tests and drew corresponding conclusions:

[0051] (1) The results of the test on 100 samples from patients with cystic hepatic echinococcosis and 29 healthy controls showed that the IgG galactosylation index Gal has high specificity, sensitivity and accuracy in the sensitive screening of cystic hepatic echinococcosis;

[0052] (2) The results of the test on 26 samples from patients with alveolar echinococcosis and 29 healthy controls showed that the IgG galactosylation index Gal has high specificity, sensitivity and accuracy in the sensitive screening of alveolar echinococcosis.

[0053] (3) The results of the test on samples from 100 patients with cystic hepatic echinococcosis and 26 patients with alveolar hepatic echinococcosis showed that the IgG galactosylation index Gal has high specificity, sensitivity and accuracy in the differential diagnosis of cystic and alveolar hepatic echinococcosis.

[0054] (4) Samples from 26 patients with alveolar echinococcosis and 24 patients with liver cancer were tested, demonstrating that the IgG galactosylation indicator Gal has high specificity, sensitivity, and accuracy in the differential diagnosis of alveolar echinococcosis and liver cancer.

[0055] The present invention has the following advantages:

[0056] (1) Applicable to the diagnosis and differentiation of cystic and alveolar hepatic echinococcosis;

[0057] (2) It can be used to differentiate alveolar hepatic echinococcosis and liver cancer, which are often confused by ultrasound imaging.

[0058] (3) The test is convenient and time-saving; the test has good repeatability for a single sample; and high-throughput testing is possible. BRIEF DESCRIPTION OF THE DRAWINGS

[0059] Figure 1 This is an example of a Gal structure.

[0060] Figure 2 This is the mass spectrum of serum IgG biantennary complex N-glycan terminal galactosylation.

[0061] Figure 3 This is the ROC curve for the diagnosis of serum IgG galactosylation index Gal in patients with hepatic echinococcosis (cystic and alveolar types).

[0062] Figure 4 This is the ROC curve for distinguishing serum IgG galactosylation index Gal between patients with alveolar hepatic echinococcosis and patients with liver cancer.

[0063] The present invention will be further described in detail below in conjunction with specific embodiments so that those skilled in the art can more clearly understand the present invention. However, the following content should not be construed as limiting the scope of protection of the claims of the present invention.

[0064] Example 1

[0065] The IgG N-glycans in the sera of 100 patients with cystic hepatic echinococcosis, 26 patients with alveolar hepatic echinococcosis, 24 patients with liver cancer and 29 healthy controls were detected using a screening method containing the IgG galactosylation index Gal. The IgG galactosylation index Gal with a certain discriminatory ability was finally determined through the calculation and analysis of the terminal galactosylation index Gal of the IgG biantennary complex N-glycan.

[0066] The chemical reagents and solvents used in the examples were of analytical grade.

[0067] 1. Case sample

[0068] (1) A total of 126 patients with echinococcosis were included between 2014 and 2016, including 100 patients with cystic hepatic echinococcosis (CE) and 26 patients with alveolar hepatic echinococcosis (AE), all of whom were diagnosed by ultrasound pathological imaging and confirmatory serological tests;

[0069] (2) 24 patients with liver cancer, all diagnosed by pathology, CT and tumor marker testing;

[0070] (3) 29 healthy subjects who underwent physical examinations, all of whom had no tumors or recent inflammation and whose Epstein-Barr virus and trematode tests were negative.

[0071] (II) Experimental operation steps

[0072] (1) Purification of serum IgG: Use the Thermo Fisher Scientific Protein A spin plate for high-throughput IgG purification. The specific process is as follows:

[0073] a. After the 96-well purification enrichment plate was equilibrated in the elution solution and the binding solution for 30 minutes at room temperature, it was centrifuged at 500 g for 2 minutes. The operation was repeated 1 to 2 times.

[0074] b. After mixing 50ul of serum and 100ul of binding solution, transfer to a 96-well purification enrichment plate and incubate at room temperature for 60 minutes; the enrichment plate after binding with IgG was first centrifuged at 500g for 2 minutes, the sample solution was collected, and the sample loading was repeated 1 to 2 times;

[0075] c. Finally, place the enrichment plate on the collection plate, add 300ul of binding solution to each well for washing, centrifuge at 500g for 2 minutes, and repeat this step 3 times;

[0076] d. Add 20ul of equilibration buffer to the collection plate, place the enrichment plate on a new collection plate, and add 200ul of elution solution to each well. Incubate for 5 minutes, centrifuge at 500g for 2 minutes, collect the purified IgG protein, and detect the sample concentration using a BCA kit.

[0077] (2) Separation and purification of N-glycans

[0078] a, Glycosidase treatment was used to separate N-glycans from IgG; the purified IgG sample was mixed with PNGaseF enzyme at a ratio of (1:1000, m / m) and enzymatically hydrolyzed at 37°C for 12 to 24 hours;

[0079] b. After activating the 96-well plate containing ZIC-HILIC filler with pure water, the 96-well plate containing ZIC-HILIC filler was equilibrated with an 80% acetonitrile aqueous solution containing 0.1% trifluoroacetic acid for 10 minutes, and the IgG N sugar chains obtained by the above enzymatic hydrolysis were transferred to the 96-well plate and incubated for 1 hour; after washing three times with an 80% acetonitrile aqueous solution with 0.1% trifluoroacetic acid, the sugar chains were finally eluted twice with a 10% acetonitrile aqueous solution containing 0.05% trifluoroacetic acid and the eluate was collected.

[0080] (3) Fluorescently labeled N-glycans

[0081] The above sugar chain samples were dissolved in a 7:3 (v / v) mixed solution of dimethyl sulfoxide and glacial acetic acid, and 50 μL of 5 mM 2-aminobenzamide and 10 mM sodium cyanoborohydride were quickly added thereto and vortexed evenly; after reacting at 65°C for 2 h, 50 μL of water was added to terminate the labeling reaction, and the mixture was centrifuged for 10 minutes. The purified derivatized sugar chains were dried and analyzed by ultra-performance liquid chromatography.

[0082] (4) Matrix-assisted laser desorption / mass spectrometry analysis of fluorescently labeled N-glycans

[0083] Instrument and parameter settings: A 5800 proteomics analyzer (Applied Biosystems, Framingham, MA, USA) was used; the instrument was equipped with a 355 nm Nd:YAG laser, an accelerating voltage of 20 kV, and a laser pulse frequency of 400 Hz; the operation mode was reflectron positive ion mode, the scanning range was set according to the actual situation, and each mass spectrum was accumulated from 1000 subspectra; the horse myoglobin trypsin-digested peptide was used as an external standard for mass calibration.

[0084] (5) Data analysis

[0085] Data Explorer 4.5 software was used for data collection and processing. The terminal galactose G0 of the biantennary complex N-glycan of blood IgG was calculated according to the corresponding intensity of the target peak in the spectrum, and the surface galactosylation degree index of IgG abundance was calculated according to the calculation formula: Gal ratio = G0 / (G1+2G2). The corresponding peaks of the terminal galactose G0, monolactose and disaccharide chains of the biantennary complex N-glycan of blood IgG were confirmed according to the previous mass spectrometry tandem method. All data were statistically analyzed using SPSS 25.

[0086] (III) Experimental results

[0087] (1) The chromatographic peak of serum IgG N sugar chain is Figure 2 , in which the end of the biantennary complex N-glycan of blood IgG is degalactose [G0+Na] + (m / z=1485.49Da)with monolactose[G1+Na] + (m / z=1647.53Da) and double lactose chain [G2+Na] + (m / z=1809.57Da); IgG surface galactosylation index Gal is shown in Table 1;

[0088] Table 1. Galactosylation index of serum IgG surface in each group

[0089] .

[0090] (2) Serum IgG surface galactosylation index Gal distinguishes hepatic echinococcosis (cystic and alveolar) groups from normal healthy groups

[0091] Serum IgG surface galactosylation index Gal was used to distinguish between the cystic hepatic echinococcosis group and the normal healthy group: if the serum IgG surface galactosylation index Gal in the cystic hepatic echinococcosis group was higher than the normal healthy group range (e.g. 5% to 50% or any point or sub-range within the range), the possibility of cystic hepatic echinococcosis in the subject was determined; the analysis results of the receiver operating characteristic curve (ROC) showed that the AUC of the IgG galactosylation index Gal was 0.8610 (95%CI: 0.7851-0.9370), the sensitivity was 87.0%, and the specificity was 93.1% (see Figure 3 ); The results showed that the serum IgG galactosylation index Gal could well distinguish the cystic hepatic echinococcosis group from the healthy group, and this index could be used for the diagnosis of cystic hepatic echinococcosis.

[0092] Serum IgG surface galactosylation index Gal was used to distinguish the alveolar hepatic echinococcosis group from the normal healthy group: if the serum IgG surface galactosylation index Gal in the alveolar hepatic echinococcosis group was higher than the normal healthy group range (e.g. 5% to 50% or any point or sub-range within the range), it was determined that the subject had the possibility of alveolar hepatic echinococcosis; the analysis results of the receiver operating characteristic curve (ROC) showed that the AUC of the IgG surface galactosylation index Gal was 0.9814 (95%CI: 0.9552-1.008), with a higher sensitivity of 100% and specificity of 100% (see Figure 3 ). The results showed that the serum IgG surface galactosylation index Gal can well distinguish the alveolar hepatic echinococcosis group and the healthy group, and this index can be used for the diagnosis of alveolar hepatic echinococcosis.

[0093] Serum IgG surface galactosylation index Gal was used to differentiate between the cystic hepatic echinococcosis group and the alveolar hepatic echinococcosis group: if the serum IgG surface galactosylation index Gal in the alveolar hepatic echinococcosis group was higher than the range of the cystic hepatic echinococcosis group (e.g., 5% to 50% or any point or sub-range within the range), the possibility of the subject having alveolar hepatic echinococcosis was determined; the analysis results of the receiver operating characteristic curve (ROC) showed that the AUC of the IgG surface galactosylation index Gal was 0.8346 (95% CI: 0.7457-0.9236), and the sensitivity and specificity were 92.3% and 83.3%, respectively (see Figure 3 ). The results showed that the serum IgG surface galactosylation index Gal can well distinguish the cystic hepatic echinococcosis group from the alveolar hepatic echinococcosis group, and this index can be used for the differential diagnosis of cystic hepatic echinococcosis and alveolar hepatic echinococcosis.

[0094] (3) Serum IgG surface galactosylation index Gal distinguishes the alveolar hepatic echinococcosis group and the liver cancer group

[0095] Serum IgG surface galactosylation index Gal was used to distinguish the alveolar hepatic echinococcosis group and the liver cancer group: the serum IgG surface galactosylation index Gal in the alveolar hepatic echinococcosis group was higher than that in the liver cancer group (for example, the average value of the index Gal in the alveolar hepatic echinococcosis group was 1.656±0.2201, while the average value in the liver cancer group was 0.3343±0.02699), which determined the possibility of the subject having alveolar hepatic echinococcosis; the analysis results of the receiver operating characteristic curve (ROC) showed that the AUC of the IgG surface galactosylation index Gal was 0.9904 (95%CI: 0.9697-1.011), the sensitivity was 100%, and the specificity was 100% (see Figure 4 ). The results showed that serum IgG surface galactosylation index Gal can well distinguish the alveolar hepatic echinococcosis group from the liver cancer group. This index can be used for the differential diagnosis of alveolar hepatic echinococcosis and liver cancer that are confused by ultrasound imaging.

Claims

1. A marker for identifying hepatic echinococcosis, specifically a galactose index at the terminal of a biantennary complex N-sugar chain on the surface of blood IgG, denoted as Gal, wherein: Gal=G0 / (G1+2G2), G0 represents the biantennary complex N-sugar chain HexNAc(4)Hex(3)Fuc(1), G1 represents the biantennary complex N-sugar chain HexNAc(4)Hex(4)Fuc(1), G2 represents the biantennary complex N-sugar chain HexNAc(4)Hex(5)Fuc(1), HexNAc represents N-acetylglucosamine, Hex represents hexose, and Fuc represents fucose; the hepatic echinococcosis includes cystic and alveolar types.

2. A product for identifying hepatic echinococcosis and distinguishing alveolar hepatic echinococcosis from liver cancer based on the marker of claim 1, the product being a kit, a device, an operating system and / or a combination thereof, the product comprising: (A) A reagent, instrument and / or system for determining the terminal galactosylation of biantennary complex N-glycan chains on the surface of blood immunoglobulin G, which is used to determine biantennary complex N-glycan chains G0 with no galactose linkage at the terminal of IgG surface, biantennary complex N-glycan chains G1 with one galactose linkage at the terminal, and biantennary complex N-glycan chains G2 with two galactose linkages at the terminal; (B) a module and / or processor for calculating Gal; (C) Modules and / or processors for Gal-based differentiation of patients with hepatic echinococcosis from healthy controls and patients with alveolar hepatic echinococcosis from liver cancer.

3. The product according to claim 2, characterized in that Also includes one or more selected from the following groups: (a) Reagents and / or instruments for collecting and / or processing blood samples from subjects; (b) reagents and / or instruments for collecting and / or purifying serum and / or plasma samples from subjects; (c) Reagents and / or instruments for collecting and / or purifying serum and / or plasma IgG from subjects; (d) Reagents and / or instruments for separating, purifying and / or enriching serum / plasma IgG surface N-glycans; (e) Reagents and / or instruments for labeling IgG surface N-glycans; (f) a database, module and / or processor for storing and / or processing the ratio of the abundance of terminal degalactose of biantennary complex N-glycans to monolactose and dilactose chains in the blood of a subject as an indicator of the degree of IgG surface galactosylation; (g) A module and / or processor for determining hepatic echinococcosis based on blood immunoglobulin G galactosylation index and for distinguishing patients with alveolar hepatic echinococcosis and liver cancer; (h) A module and / or processor for providing test results and / or reports.

4. A module for identifying hepatic echinococcosis based on the markers of claim 1, characterized in that: include: (i) Hepatic echinococcosis and healthy control identification submodule: When the blood IgG galactosylation index Gal is higher than the pre-set range, it is determined that the subject is likely to have hepatic echinococcosis; (ii) A submodule for differential diagnosis of cystic hepatic echinococcosis and alveolar hepatic echinococcosis: when the blood IgG galactosylation index Gal is higher than the pre-serum IgG galactosylation index Gal range for cystic hepatic echinococcosis, it is determined that the subject is likely to have alveolar hepatic echinococcosis; (iii) Submodule for differential diagnosis of alveolar hepatic echinococcosis and liver cancer: When the blood IgG galactosylation index Gal is higher than the pre-set range of serum IgG galactosylation index Gal in the liver cancer group, it is determined that the subject is likely to have alveolar hepatic echinococcosis.

5. A system for identifying hepatic echinococcosis based on the markers of claim 1, characterized in that: include: (a) a blood sample collection module, used to collect and / or process a blood sample of a subject; (b) a blood sample purification module, used for collecting and / or purifying serum and / or plasma samples of a subject; (c) an IgG collection and / or purification module, used for collecting and / or purifying serum and / or plasma IgG from a subject; (d) an IgG surface N-glycan separation and purification module, used for separating, purifying and / or enriching serum / plasma IgG surface N-glycans; (e) a labeling module for labeling N-glycans on the surface of IgG; (f) a storage module for storing and / or processing the ratio of the abundance of biantennary complex N-glycans terminally degalactose to monolactose and dilactose chains in the blood of the subject as an indicator of the degree of galactosylation on the surface of IgG; (g) an identification module, used to determine hepatic echinococcosis and to differentiate patients with alveolar hepatic echinococcosis and liver cancer based on blood immunoglobulin G galactosylation indicators; It includes: Gal calculation module and discrimination module; Gal calculation module is used to calculate the blood immunoglobulin G galactosylation index Gal; the discrimination module uses Gal to identify the status of hepatic echinococcosis: (1) Gal distinguishes the hepatic echinococcosis group from the normal healthy group: Gal distinguishes the cystic hepatic echinococcosis group and the normal healthy group: if the serum IgG surface galactosylation index Gal in the cystic hepatic echinococcosis group is higher than that in the normal healthy group, it is determined that the subject may have cystic hepatic echinococcosis; Gal distinguishes the alveolar hepatic echinococcosis group and the normal healthy group: if the serum IgG surface galactosylation index Gal in the alveolar hepatic echinococcosis group is higher than that in the normal healthy group, it is determined that the subject may have alveolar hepatic echinococcosis; (2) Gal differentiation between cystic hepatic echinococcosis group and alveolar hepatic echinococcosis group: If the serum IgG surface galactosylation index Gal in the alveolar hepatic echinococcosis group is higher than that in the cystic hepatic echinococcosis group, it is determined that the subject is likely to have alveolar hepatic echinococcosis; (3) Gal differentiation between the alveolar hepatic echinococcosis group and the liver cancer group: If the serum IgG surface galactosylation index Gal in the alveolar hepatic echinococcosis group is higher than that in the liver cancer group, it is determined that the subject is likely to have alveolar hepatic echinococcosis; (h) A display module, used to display and provide test results and / or reports.

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