CN117517675A - Application of protein biomarker SAA2 in clinical diagnosis of Crohn disease - Google Patents
Application of protein biomarker SAA2 in clinical diagnosis of Crohn disease Download PDFInfo
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Abstract
The invention belongs to the technical field of clinical medicine, and discloses application of a reagent for detecting protein biomarker SAA2 expression level in preparation of a Crohn disease clinical diagnosis kit, wherein when the protein biomarker SAA2 expression level in peripheral blood serum of a subject is increased, the subject is indicated to suffer from Crohn disease. In addition, the invention also provides a kit for clinical diagnosis of the Crohn disease, a module for clinical diagnosis of the Crohn disease and a method for screening medicines for treating the Crohn disease. The CD serum diagnosis marker with high sensitivity and specificity provided by the invention can be used for early diagnosis of CD clinically so as to guide the treatment process of CD clinically and provide a new theoretical basis for further explaining pathophysiology pathogenesis of CD.
Description
The application is a divisional application of patent application with the application date of 2022, 9 and 23, the application number of 202211168032.3 and the name of 'application of a serological biomarker in clinical diagnosis of Crohn disease'.
Technical Field
The invention belongs to the technical field of clinical medicine, and particularly relates to application of a group of serological biomarkers in clinical diagnosis of Crohn's disease.
Background
Inflammatory bowel disease (inflammatory bowel disease, IBD) is a chronic, non-specific inflammatory bowel disease whose etiology is not yet fully defined, and currently the dominant view is mainly to the intestinal inflammatory lesions caused by imbalance of intestinal immune homeostasis of individuals due to the influence of a number of factors such as environment, diet, drugs, intestinal flora, etc., in individuals with genetic susceptibility, including Crohn's Disease (CD) and ulcerative colitis (ulcerative colitis, UC). The clinical symptoms of CD mainly show abdominal pain, diarrhea, abdominal mass, anus Zhou Louguan and the like, and lesions are distributed in multiple sections and in a jumping manner, so that intestinal obstruction, stenosis, perforation and the like are often caused, and serious intestinal disability is caused. The disease is repeated and persisted, the incidence rate of the young and the middle-aged is increased year by year, and the clinic lacks sensitive early diagnosis methods and effective treatment means, and the like, which bring heavy burden to individuals, families and society, so the disease is also called green cancer. At present, the clinical diagnosis method for CD mainly comprises endoscopy and biopsy histopathological diagnosis, has larger traumatism, brings larger pain to patients, has relatively higher cost and is inconvenient in clinical application; imaging is of lower diagnostic value for CD and serum and stool biomarker specificity or sensitivity. The early diagnosis and early treatment have great benefits for prognosis of CD patients, so that the method searches for convenient and effective serum biomarkers and has important significance in the processes of CD clinical diagnosis, treatment and prognosis management.
The extent of disease activity in CD patients is assessed in the prior art by detecting the level of CRP in the peripheral blood of CD patients. CRP is a serological marker of nonspecific acute inflammation, is mainly synthesized by liver cells, is acute real phase response protein which can be detected in blood plasma when an organism is infected and damaged by tissues, has close correlation with inflammatory factors, has strong positive correlation with clinical activity of CD, and can be used for distinguishing IBD from other non-inflammatory gastrointestinal diseases. CRP is a nonspecific inflammatory marker, and in many inflammatory conditions, including infection and other diseases that cause inflammatory injury to tissues, has low specificity, and can only be used for evaluating the systemic inflammatory response level of patients when CD occurs, to a certain extent, the activity level of the patient's diseases, and cannot provide assistance for accurate diagnosis of CD. And despite some CD patients in clinical activity, CRP may still be shown to be at sustained low levels, including low BMI or plain ileum CD patients.
Furthermore, the prior art has also diagnosed Crohn's disease by detecting anti-microbial related antibodies (e.g., ASCA, cbir1, OMPC) in the peripheral blood of CD patients. Anti-polysaccharide antibodies are a class of antibodies directed against microbial (bacterial, fungal) cell wall polysaccharide epitopes, which have been accepted by most clinicians as CD-associated specific serological markers, with the serum-reactive antibody ASCA directed against saccharomyces cerevisiae cell wall mannans being the first serological marker found to be highly specific for CD. The level of ASCA in the peripheral blood of IBD patients is currently tested clinically to assess the disease behaviour and disease activity of IBD patients. However, studies have shown that these antimicrobial-related antibodies have a general disadvantage in terms of low sensitivity, low positive detection rate, or low specificity for CD diagnosis.
Terminology:
1. inflammatory bowel disease, english name inflammatory bowel disease, abbreviated IBD.
2. Crohn's disease, abbreviated as CD.
3. Plasma Amyloid-2, english name Serum amylase A2, abbreviated SAA2.
4. Insulin-like growth factor binding protein-2, english name Insulin Like Growth Factor Binding Protein, abbreviated IGFBP2.
5. Golgi membrane protein-1, english name Golgi Membrane Protein, abbreviated GOLM1.
6. Dipeptidyl peptidase-4, english name Dipeptidyl Peptidase, abbreviated DPP4.
7. Guanylate binding protein-1, english name Guanylate Binding Protein, abbreviated GBP1.
8. "biomarker", herein or herein can be written as "marker" or "serological marker", including DNA, RNA, protein, carbohydrate or glycolipid based molecular markers, herein referred to as soluble protein molecular markers in serum, whose presence can be detected in a subject or patient's peripheral serum sample by standard methods (methods referred to herein).
9. "sample" refers to a peripheral serum specimen derived from a CD patient or healthy subject, and can be obtained by known techniques.
Disclosure of Invention
The invention aims to provide a set of CD serum diagnosis marker sets with high sensitivity and specificity, which are used for early diagnosis of CD clinically so as to guide the treatment process of CD clinically and provide a new theoretical basis for further explaining the pathophysiology pathogenesis of CD.
In the early work, we collected 30 CD patients surgically resected the inflammatory and relatively normal tissues of ileal bowel segment samples, including intestinal mucosa layer (MUC), submucosa-myometrium-serosa layer (SMS), paracented adipose tissue (MAT), mesentery (MES) and Mesenteric Lymph Nodes (MLN), and 5 non-CD patients (NC) corresponding relatively normal tissues (this 5 control group of patients were early ascending colon tumor patients, the ascending colon and terminal ileal bowel segments were surgically resected, the samples were backed up and subjected to immunopathological examination, and two or more specialized pathologists re-examined as non-tumor affected relatively normal tissues). We first performed proteomic sequencing and 16S rRNA sequencing analysis studies on the above samples, depicting the protein molecular and bacterial spectra of different tissue sites during CD intestinal inflammation. Then, according to the change condition of the relative expression quantity of the differential protein molecules at different tissue parts of the CD patient and the change condition of the relative expression quantity of the differential strain related genes at different tissue parts of the CD patient, the c-Fuzzy map is drawn, and a statistical analysis method shows that the P.C1 (protein cluster 1) and the M.C1 (microbial cluster 1) have stronger correlation. After correlation analysis and functional annotation are carried out on protein molecules in P.C1 and bacterial genes in M.C1, a series of key differential protein molecules and key strains are identified, and the important roles are played in the process of spreading intestinal inflammation to extra-intestinal tissues and shifting of flora to extra-intestinal tissues in the process of CD intestinal inflammation.
According to the results of our earlier work, we considered that the disturbance of immune regulation and the destruction of physical barrier function in different tissues of the intestinal tract and its accessory organs during the CD intestinal inflammation occurrence process may be involved in the process of spreading intestinal inflammation to the extra-intestinal tissues and flora shift during CD occurrence, so we speculate whether the above key protein molecules and key strains can have diagnostic efficacy in CD patient body fluid samples. Thus, we collected 30 CD patients and 30 healthy controls paired peripheral serum and stool samples, respectively subjected to serum non-targeted proteomic sequencing and stool 16S rRNA sequencing analysis, and compared with histology and bacteriology results, found that 5 of the above key protein molecules were differentially expressed in CD patient peripheral serum, including SAA2, DPP4, GOLM1, IGFBP2, and GBP1, and that the key protein molecules and the key species in stool had good correlation.
Based on this, the first aspect of the invention proposes the use of a set of serological biomarkers comprising at least one of SAA2, DPP4, GOLM1, IGFBP2 or GBP1 protein molecules in the clinical diagnosis of Crohn's disease.
According to the application provided by the invention, whether the subject suffers from Crohn disease is judged by detecting the expression level of the serum biomarker in the peripheral blood serum of the subject.
In particular, when the expression level of at least one of SAA2, GOLM1, IGFBP2, or GBP1 in the subject's peripheral blood serum is elevated, the subject is indicated to have crohn's disease; when the level of DPP4 expression in the peripheral blood serum of a subject is reduced, the subject is indicated to have crohn's disease.
In a second aspect, the invention provides a kit for clinical diagnosis of crohn's disease, the kit comprising reagents for detecting the expression level of a serological biomarker comprising at least one of a SAA2, DPP4, GOLM1, IGFBP2 or GBP1 protein molecule.
Preferably, in the kit for clinical diagnosis of crohn's disease provided by the present invention, the reagent for detecting the expression level of the serological biomarker includes: and (3) detecting the expression level of the serologic biomarker based on RT-PCR, real-time quantitative PCR, immunodetection, in situ hybridization, chip or high-throughput sequencing.
Further preferably, the reagent for detecting the expression level of the serum biomarker based on RT-PCR comprises at least a pair of primers specifically amplifying the nucleic acid sequence of the serum biomarker; the reagent for detecting the expression level of the serum biological marker based on real-time quantitative PCR comprises at least one pair of primers for specifically amplifying the nucleic acid sequence of the serum biological marker; the reagent for detecting the expression level of the serum biomarker based on the immunodetection technology at least comprises an antibody which specifically binds to the serum biomarker; the reagent for detecting the expression level of the serological biomarker based on in situ hybridization comprises at least a probe hybridized with a nucleic acid sequence of the serological biomarker; the chip-based reagent for detecting the expression level of the serological biomarker at least comprises: protein chip and gene chip; the protein chip comprises an antibody which specifically binds to the serological biomarker, and the gene chip comprises a probe hybridized with a nucleic acid sequence of the serological biomarker; the reagent for detecting the expression level of the serum biomarker based on high-throughput sequencing at least comprises: primers and/or probes for detecting the transcriptional level of the serological biomarker.
A third aspect of the invention provides a module for clinical diagnosis of crohn's disease, the module comprising a diagnostic index input module and a crohn's disease condition assessment module; the diagnostic index input module at least comprises means for obtaining the expression level of a serological biomarker in the peripheral blood serum of a subject, wherein the serological biomarker comprises at least one of SAA2, DPP4, GOLM1, IGFBP2 or GBP1 protein molecules; the Crohn disease state evaluation module at least comprises a step of inputting the expression level of the serological biomarker in the peripheral blood serum of the subject, which is obtained by the diagnosis index input module, into a diagnosis model to obtain a score value; comparing the obtained score value with a preset cut-off value of a diagnosis model, and outputting an evaluation result of the Crohn disease state of the subject; the state of Crohn's disease comprises a Crohn's disease-related state preset by a diagnostic model.
In a fourth aspect, the invention provides a method for screening for a drug for the treatment of Crohn's disease comprising: detecting the expression level V1 of a serological biomarker in a sample derived from a subject in a test group using a test drug to the subject; detecting the expression level V2 of a serological biomarker in a sample derived from a subject in a control group using a blank control drug to the subject; comparing the detected serological biomarkers V1 and V2 to determine whether the test drug has efficacy in treating crohn's disease; the serological biomarker comprises at least one of SAA2, DPP4, GOLM1, IGFBP2 or GBP1 protein molecules.
Drawings
FIG. 1 is a comparison of IGFBP2, DPP4, GBP1, SAA2 and GOLM1 expression levels in peripheral serum of patients with Crohn's disease and healthy controls, wherein HC refers to healthy controls and A-CD refers to active CD patients;
FIG. 2 is a ROC graph of SAA2 as a marker for diagnosing Crohn's disease and compared to CRP;
FIG. 3 is a ROC graph of GBP1 as a marker for diagnosing Crohn's disease and compared to CRP;
FIG. 4 is a ROC graph of IGFBP2 as a marker for diagnosis of Crohn's disease and compared to CRP;
FIG. 5 is a ROC graph of GOLM1 as a marker for diagnosing Crohn's disease and compared to CRP;
FIG. 6 is a ROC graph of DPP4 as a marker for diagnosis of Crohn's disease, and compared with CRP;
FIG. 7 is a graph of the average ROC of SAA2, DPP4, IGFBP2, GOLM1 and GBP1 as markers for diagnosing Crohn's disease and compared to CRP;
FIG. 8 is an analysis of the correlation degree of SAA2 with CRP expression level in the peripheral serum of patients suffering from Crohn's disease;
FIG. 9 is an analysis of the correlation degree of GBP1 with CRP expression level in the peripheral serum of a patient suffering from Crohn's disease;
FIG. 10 is an analysis of the correlation degree of IGFBP2 with CRP expression level in peripheral serum of patients suffering from Crohn's disease;
FIG. 11 is an analysis of the degree of correlation of GOLM1 with CRP expression level in the peripheral serum of patients suffering from Crohn's disease;
FIG. 12 is an analysis of the degree of correlation of DPP4 with CRP expression level in the peripheral serum of patients suffering from Crohn's disease.
Detailed Description
In order to make the objects, technical solutions and advantages of the present invention more apparent, embodiments of the present invention will be described in detail below. However, those of ordinary skill in the art will understand that in various embodiments of the present invention, numerous technical details have been set forth in order to provide a better understanding of the present application. However, the technical solutions claimed in the claims of the present application can be realized without these technical details and various changes and modifications based on the following embodiments.
1. Discovery of biomarkers: sequencing analysis study of Crohn's disease and non-Crohn's disease intestinal tract and its accessory organ proteomics and bacteriology
1.1 sample collection:
screening age >18 years old, not using immunosuppressant, small molecule targeting drug, glucocorticoid, antibiotic and other special drugs, etc., not combining other diseases affecting intestinal pathophysiological state, not combining patients with diseases such as hypertension, diabetes, etc., acquiring patient's informed consent in advance, collecting 30 cases of inflammation and relatively normal intestinal mucosa layer, submucosa-myoma-serosa layer, periintestinal fat, mesenteric and mesenteric lymph node of Crohn's disease patient under aseptic condition by professional operation doctor in the operation process of patient, and preserving 5 cases of relatively normal mucosa layer, submucosa-myoma-serosa layer, periintestinal fat, mesenteric and mesenteric lymph node of non-Crohn's disease affected part at-80 ℃ for standby. The non-CD patient is subjected to pathological histology examination relative to the normal part tissues, and more than two professional pathologists review the non-CD patient as non-disease invasion tissues.
1.2 histology sequencing analysis:
(1) 4-D proteomic sequencing analysis was performed using CD patient surgically resected intestinal tract and its attendant tissue samples (including paired inflammatory and relatively normal site intestinal mucosal tissue, myometrium and serosal tissue, paracentesis adipose tissue, mesenteric tissue and mesenteric lymph node tissue) and non-CD patient surgically resected intestinal tract and its attendant tissue samples (including intestinal mucosal tissue, myometrium and serosal tissue, paracentesis adipose tissue, mesenteric tissue and mesenteric lymph node tissue).
(2) Comparing the difference of protein expression profiles in tissue samples of the same type of inflammation and non-CD patient relative to the normal part of the CD patient, calculating the expression quantity of the differential protein in the tissue samples, carrying out channel enrichment analysis on the differential protein, carrying out functional annotation on the differential protein according to a database (Nano string, report and the like), exploring the change condition of the protein expression profiles in different tissues when CD intestinal inflammation occurs, and exploring the change of biological functions of different tissues.
(3) Comparing the difference of bacterial spectrums in tissue samples of the same type between the inflammation part and the relative normal part of a CD patient, calculating the expression quantity of differential proteins in the tissue samples, and exploring the influence of the local inflammation of intestinal tracts on the protein expression spectrum when CD occurs.
(4) And (3) drawing protein interaction network diagrams in different tissue samples of the inflammation part of the CD patient, and analyzing key protein molecules and interaction relations in different parts when CD intestinal inflammation occurs.
1.3 tissue bacteriological sequencing analytical study:
the bacterial spectrum of tissues of different parts of the intestinal tract and the accessory organs of a CD patient when enteritis occurs is depicted.
(1) 16S rDNA bacteriological sequencing analysis was performed using CD patient surgically resected intestinal tract and its attendant tissue samples (including paired inflammatory and relatively normal site intestinal mucosal tissue, myometrium and serosal tissue, paracentesis adipose tissue, mesenteric tissue and mesenteric lymph node tissue) and non-CD patient surgically resected intestinal tract and its attendant tissue samples (including intestinal mucosal tissue, myometrium and serosal tissue, paracentesis adipose tissue, mesenteric tissue and mesenteric lymph node tissue).
(2) Comparing the difference of the bacterial spectrum in the tissue sample of the same type of the inflammation of the CD patient and the non-CD patient relative to the normal part, calculating the abundance of the differential strain in the tissue sample, and exploring the change condition of the bacterial spectrum of the intestinal tract and the accessory organs when the CD enteritis occurs.
(3) Comparing the difference of the bacterial spectrum in the tissue sample of the same type between the inflammation part of the CD patient and the relative normal part, calculating the abundance of the differential strain in the tissue sample, and exploring the influence of the local inflammation of the intestinal tract on the bacterial spectrum when the CD occurs.
(4) Longitudinally comparing the abundance of the differential strain in different tissue samples of the inflammation part of the CD patient, calculating and simulating the possible sources of the formation of specific flora spectra of different parts by using a bioinformatics method, and exploring the flora shift and the spatial distribution condition in intestinal tracts and the tissues of accessory organs when the CD occurs.
(5) And (3) drawing a network chart of interactions of flora in different tissue samples of the inflammation part of the CD patient, and analyzing the spatial distribution of key bacterial strains in different parts when CD intestinal inflammation occurs.
1.4 tissue bacterial-host protein molecular interactions relationship study:
(1) drawing an abundance/expression quantity change curve graph according to the abundance and the protein expression quantity of the flora in different tissues of the intestinal tract of a CD patient and the inflammation parts of the accessory organs of the CD patient, comparing the abundance/expression quantity change curve graph, and searching for flora clusters and protein molecular clusters with similar abundance/expression quantity change trend.
(2) The bacterial flora and the protein cluster are subjected to pathway enrichment analysis, and the state of change of the host function and the influence on bacterial population in different represented tissue sites are explored.
(3) According to the conditions of flora abundance and protein expression in different tissue samples of the intestinal tract and the accessory organs of a CD patient and the existing database, a network chart of the interaction relation between bacteria and protein molecules is drawn, and strains and protein molecules which play a key role in different tissue parts when intestinal inflammation occurs are explored.
(4) The critical interaction protein molecules and strains in different tissues of intestinal tracts and the inflammatory parts of accessory organs of CD patients are longitudinally compared, and the interaction mode is explored in the flora shift process of CD enteritis.
1.5 verify the enrichment of the above key protein molecules and species in CD patient peripheral serum and feces:
collecting paired peripheral blood serum samples and fecal samples of 30 active-phase CD patients and 30 healthy controls, detecting key protein molecules found in the study by using a non-targeted proteomics technology, analyzing flora composition in the samples by using a 16S rRNA detection technology, detecting abundance of key strains found in the study, and evaluating sensitivity and specificity of the key strains as CD disease diagnosis markers; clinical information of CD patients, such as information of age, sex, disease behaviors, drug administration condition, complications and the like, is collected, and the correlation of the changes of the key protein molecules and the key strains with clinical symptoms or treatment methods of the patients is studied by using a statistical method. Finally, 5 key protein molecules which have differential expression in peripheral blood of CD patients (shown in figures 1-7) and have better correlation with corresponding strains of feces are found, and are shown in the following table 1:
TABLE 1
2. Novel biomarker diagnostic efficacy validation:
2.1 sample collection:
endoscopy is carried out on patients with Crohn disease and patients without Crohn disease (or healthy subjects), lesions of the Crohn disease are segmental or jumping, early patients are thrush-like ulcers, then the ulcer range can be expanded and fused, longitudinal fissure-like ulcers along the long axis of the intestinal tract are formed, and mucous membrane is divided into cobble-like appearance; the method is characterized in that mucosal tissues of lesion parts in intestinal tracts of patients are collected and rechecked by more than two professional pathologists, and the lesion mucosal tissues of the Crohn disease are characterized by non-cheesy granuloma consisting of epithelioid cells and multinuclear giant cells, and fissured ulcers reaching submucosa and even myometrium deeply, and are accompanied by aggregation of a large number of lymphocytes, expansion of lymphatic vessels, gangliotis and the like of the lamina propria and submucosa. Subjects can be distinguished from patients with crohn's disease and non-crohn's disease based on endoscopic and histopathological examination results.
2.2 subject peripheral serum sample collection and analysis:
the purpose of the experiment is as follows: peripheral serum samples of 30 patients suffering from Crohn's disease and 30 healthy controls were obtained, and the ELISA method was used to detect the expression levels of the above five soluble protein molecules (including SAA2, IGFBP2, GOLM1, DPP4 and GBP 1) in the CD patient peripheral serum, and compared with the expression levels of the corresponding protein molecules in the control group subjects peripheral serum samples. The control was a healthy subject who was not crohn's disease.
The experimental method comprises the following steps: enzyme-linked immunosorbent assay: coating an ELISA plate with an antibody corresponding to a target soluble protein molecule prepared in advance to prepare a solid-phase carrier; adding pre-diluted standard substances and subject serum into the antibody-coated microwells, allowing target soluble protein molecules (including SAA2, IGFBP2, GOLM1, DPP4 and GBP 1) to bind to the immobilized antibodies, washing unbound samples, adding horseradish peroxidase-labeled detection antibodies, and incubating to allow the enzyme-labeled detection antibodies to bind to target protein molecules in the subject serum, thereby immobilizing on microwell plates. After the unbound enzyme label has been washed thoroughly, it is developed with the substrate TMB. TMB forms a blue cationic product under the catalysis of peroxidase, and after termination of the reaction by adding acid, the blue color turns yellow. The shade of color and the concentration of the target soluble protein molecule in the sample are positively correlated. The OD value was measured at a wavelength of 450nm using an enzyme-labeled instrument, and the concentration of the soluble protein molecules in the sample was calculated.
Data analysis: the expression levels of the target soluble protein molecules in the peripheral blood serum of the above 30 patients with Crohn's disease and 30 healthy controls (age and sex matched between two groups of subjects) were compared, and analyzed by ROC curve and compared in clinic with a marker C-reactive protein (CRP) for evaluating disease activity of the patients with Crohn's disease, wherein the AUC value of CRP is 0.890, while the AUC value of SAA2 is 0.890, the AUC value of GBP1 is 0.902, the AUC value of IGFBP2 is 0.913, the AUC value of GOLM1 is 0.917, and the AUC value of DPP4 is 0.920.
Fig. 2 is a ROC graph of SAA2 as a marker for diagnosing crohn's disease, and compared with CRP, table 2 is a calculation of the area under the curve.
TABLE 2 area under the curve of FIG. 2
(note: test result variable: CRP has at least one junction between the positive and negative actual state sets. Statistics may deviate.
a. Under a non-parametric assumption; b. zero assumption: real area=0.5. )
Fig. 3 is a ROC graph of GBP1 as a marker for diagnosing crohn's disease, and compared with CRP, table 3 is a calculation of the area under the curve.
TABLE 3 area under the curve of FIG. 3
(note: test result variable: CRP has at least one junction between the positive and negative actual state sets. Statistics may deviate.
a. Under a non-parametric assumption; b. zero assumption: real area=0.5. )
Fig. 4 is a ROC graph of IGFBP2 as a marker for diagnosis of crohn's disease and compared with CRP, and table 4 is a calculation of the area under the curve.
TABLE 4 area under the curve of FIG. 4
(note: test result variable: CRP has at least one junction between the positive and negative actual state sets. Statistics may deviate.
a. Under a non-parametric assumption; b. zero assumption: real area=0.5. )
Fig. 5 is a ROC graph of GOLM1 as a marker for diagnosing crohn's disease, and compared with CRP, table 5 is a calculation of the area under the curve.
TABLE 5 area under the curve of FIG. 5
(note: test result variable: CRP has at least one junction between the positive and negative actual state sets. Statistics may deviate.
a. Under a non-parametric assumption; b. zero assumption: real area=0.5. )
FIG. 6 is a ROC graph of DPP4 as a marker for diagnosis of Crohn's disease, and compared with CRP, calculation of area under the graph.
TABLE 6 area under the curve of FIG. 6
(note: test result variable: CRP has at least one junction between the positive and negative actual state sets. Statistics may deviate.
a. Under a non-parametric assumption; b. zero assumption: real area=0.5. )
FIG. 7 is an average ROC graph of SAA2, DPP4, IGFBP2, GOLM1 and GBP1 as markers for diagnosing Crohn's disease and compared with CRP.
The correlation between the target soluble protein molecules and CRP in the peripheral serum of patients with crohn's disease was then compared. FIG. 8 is an analysis of the correlation degree of SAA2 with CRP expression level in the peripheral serum of patients suffering from Crohn's disease; FIG. 9 is an analysis of the correlation degree of GBP1 with CRP expression level in the peripheral serum of a patient suffering from Crohn's disease; FIG. 10 is an analysis of the correlation degree of IGFBP2 with CRP expression level in peripheral serum of patients suffering from Crohn's disease; FIG. 11 is an analysis of the degree of correlation of GOLM1 with CRP expression level in the peripheral serum of patients suffering from Crohn's disease; FIG. 12 is an analysis of the degree of correlation of DPP4 with CRP expression level in the peripheral serum of patients suffering from Crohn's disease. All had significance according to statistical analysis (p values were all less than 0.01), with a correlation coefficient value of SAA2 to CRP of 0.906, a correlation coefficient value of golm1 to CRP of 0.556, a correlation coefficient value of igfbp2 to CRP of 0.137, a correlation coefficient value of gbp1 to CRP of 0.411, all being significant positive correlations; the correlation coefficient value of DPP4 with CRP is-0.527, which is a significant negative correlation.
Based on the research results, the invention provides that one or more of SAA2, DPP4, GOLM1, IGFBP2 or GBP1 protein molecules can be used as a serological biomarker for clinical diagnosis of Crohn's disease.
It will be understood by those of ordinary skill in the art that the foregoing embodiments are specific examples of carrying out the invention and that various changes in form and details may be made therein without departing from the spirit and scope of the invention.
Claims (8)
1. Use of a reagent for detecting the expression level of a protein biomarker SAA2 in the preparation of a clinical diagnosis kit for Crohn's disease, wherein the kit judges whether the subject suffers from Crohn's disease by detecting the expression level of the protein biomarker SAA2 in the serum of the peripheral blood of the subject.
2. The use of claim 1, wherein an increase in the level of expression of the protein biomarker SAA2 in the peripheral blood serum of the subject is indicative of the subject suffering from crohn's disease.
3. A kit for clinical diagnosis of crohn's disease, comprising reagents for detecting the expression level of the protein biomarker SAA2 in the peripheral blood serum of a subject.
4. The kit for clinical diagnosis of crohn's disease according to claim 3, characterized in that the subject is indicated to have crohn's disease when the level of expression of the protein biomarker SAA2 in the peripheral blood serum of the subject is elevated.
5. The kit for clinical diagnosis of crohn's disease according to claim 4, wherein the reagent for detecting the expression level of the protein biomarker SAA2 in the peripheral blood serum of the subject includes: and (3) detecting the protein biomarker SAA2 expression level based on an immunodetection technology.
6. The kit for clinical diagnosis of crohn's disease according to claim 5, characterized in that the reagent for detecting the protein biomarker SAA2 expression level based on an immunodetection technique includes at least an antibody that specifically binds to the protein biomarker.
7. A module for clinical diagnosis of crohn's disease, comprising a diagnostic index input module and a crohn's disease condition assessment module;
the diagnostic index input module at least comprises the steps of obtaining the expression level of a protein biomarker SAA2 in the serum of the peripheral blood of a subject;
the Crohn's disease state evaluation module at least comprises a step of inputting the protein biomarker SAA2 expression level in the peripheral blood serum of the subject obtained by the diagnosis index input module into a diagnosis model to obtain a score value; comparing the obtained score value with a preset cut-off value of a diagnosis model, and outputting an evaluation result of the Crohn disease state of the subject; the state of Crohn's disease comprises a Crohn's disease-related state preset by a diagnostic model.
8. A method for screening for a drug for the treatment of crohn's disease, comprising:
detecting the protein biomarker SAA2 expression level V1 in a peripheral blood serum sample derived from a subject in a test group using a test drug to the subject; in a control group, using a blank control drug to a subject to be tested, and detecting the expression level V2 of the protein biomarker SAA2 in a peripheral blood serum sample derived from the subject in the control group; comparing the detected V1 and V2 to determine whether the test drug has efficacy in treating crohn's disease.
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