CN107782895A - The urine protein marker of glioma and its purposes in oncotherapy effect is monitored - Google Patents
The urine protein marker of glioma and its purposes in oncotherapy effect is monitored Download PDFInfo
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Abstract
This disclosure relates to the urine protein marker of glioma and its purposes in oncotherapy effect is monitored.Specifically, this disclosure relates to which purposes of the glioma Urine proteins mark in the therapeutic effect of monitoring Patients with gliomas, the Urine proteins mark are selected from：Thrombospondin 4, collagen α 1 (IV) chain, interleukin 1 receptor antagonist protein, ribonuclease inhibitor, N N-acetylmuramyl L ala amide enzymes, fine albumen 1, it polymerize immunoglobulin receptor, cathepsin D, bladder chalone C, Aminopeptidase N, dipeptidyl peptidase 1, β glucuronic acids, lysosome Pro X carboxypeptidases, desmin 2, selenium Binding Protein 1, the part 2 of apoptosis albumen 1, acid ceramidase, Napsin A, lysosomal associated membrane glycoprotein 1, glutamy aminopeptidase, γ glutamyl hydrolases etc..The aftertreatment effect of patient can be effectively determined using the indentifying substance of the disclosure.
Description
Technical field
This disclosure relates to clinical medicine；In particular to the related urine protein marker of human glioma.It is specific and
Speech, this disclosure relates to which the human glioma obtained using Patients with gliomas urine sample and mass spectral analysis proteomic techniques is examined
Urine protein marker disconnected and/or that monitoring is related, and application thereof.
Background technology
Disease biomarkers are the measurable changes related to pathologic process, can be used for diagnosing the illness, monitor disease
Journey, predictive disease prognosis and assessment therapeutic effect.Urine is preferable disease marker sample source, and urine can be by noninvasive
Mode largely obtain, can painlessly collect the urine of same patient's different time points repeatedly, it is often more important that in urine lack
The regulation and control of weary homeostatic mechanism can be enriched with the various change of body discharge, and these changes are exactly potential disease marker (ginseng
See Gao Y.Urine--an untapped goldmine for biomarker discovery.Sci China.Life
Sci,2013,56(12):1145)。
Urine protein group (urinary proteomics) is intended to establish a kind of noninvasive " liquid biopsy " (liquid
Biopsy) diagnostic method, by detect disease marker special in urine come part substitute organ aspiration biopsy turn into face
The important research direction of bed doctor's concern, has great potential applicability in clinical practice.
Glioma is a kind of most common primary brain tumor, accounts for the 81% of central nervous system malignant tumour.Glue
Matter knurl grade malignancy is high, disease progression it is rapid (referring to Ostrom Q T, Bauchet L, Davis F G, et al. The
epidemiology of glioma in adults:a“state of the science”review.Neuro-
oncology,2014,16(7):896-913).Central nervous system malignant tumour using glioblastoma as representative causes huge
Big social economy and family burden, it is always the focus of current tumor research.So glioma is diagnosed in time and monitors colloid
Knurl patient disease therapeutic effect is most important for the survival rate for improving patient.
The content of the invention
In view of the demand of this area, according to some of the disclosure, embodiment there is provided for selected from following albumen
Indentifying substance prepare be used for monitor subject glioma treatment effect reagent in purposes, wherein it is described identification examination
Agent：α-crystal proteins B chains, beta-glucuronic acid, CD276 antigens, the component G of c-type Lectin domain family 4, gamma-glutamyl water
Solve enzyme, N- N-acetylmuramyls-ALANINE amidase, Napsin-A, carcinomebryonic antigen relevant cell adhesion molecule 1, Aminopeptidase N,
Interleukin-1 receptor antagonist protein, visible peristalsis visible intestinal peristalsis maltose-glucoamylase, the part 2 of apoptosis albumen 1, dipeptidyl peptidase
It is enzyme 1, dihydropteridine reductase, glutamy aminopeptidase, cystatin-C, ribonuclease inhibitor, collagen α -1 (IV), poly-
Close immunoglobulin receptor, desmin -2, similar serine carboxypeptidase CPVL, annexin A7, attachment G protein coupled receptor
F5, lysosome Pro-X carboxypeptidases, lysosomal associated membrane glycoprotein 1, lysosomal associated membrane glycoprotein 2, acid ceramidase,
Fine albumen -1, mitochondria 10kDa heat shock proteins, malate dehydrogenase,mitochondrial, selenium Binding Protein 1, platelet thrombin are quick
Feel protein-4, cathepsin D, p75TNFR, and combinations thereof.
In a particular embodiment, multiple time points before subject and after treatment (at least one before treatment,
Or at least two or at least three；At least one or at least two or at least three or at least four or at least five after treatment) enter
Row sampling, the therapeutic effect situation of glioma is monitored according to the situation of change of protein marker in Urine in Patients.Technical staff
It is understood that at least gathering 1 sample before treatment, a sample is at least gathered after treatment, to be compared；Certainly, it is unlimited
In a sample, allow the variation tendency of dynamically monitoring mark thing in more time point collecting samples.However, also should not mistake
In intensive, beyond the ability to bear of subject；And excessively intensive sample collection, cause the time interval between sample too short,
Change is difficult to observe by, can also increase monitoring cost.It is appreciated that excessively remote, such as subject is not meant that " before treatment "
Not yet when illness.Therefore, before treatment, described subject should suffer from glioma after diagnosing.In some embodiments,
Refer to before treatment, receive a few days ago 0 to 72 hour for the treatment of in the subject；It is preferred that 24 to 48 hours；More preferably 12 to 24
Hour.Herein, " a few days ago 0 hour that receives treatment " refers to not yet receive but to receive treatment at once.
Refer to after treatment, the subject receive treatment day after 5 to 20 days, preferably 6 to 15 days, more preferably 7 to
14 days.
In some embodiments, (including endpoint value, in full together) gathers 1 sample in 12 to 72 hours before treatment,
And one sample of collection in 7 to 14 days after treating.
In other embodiments, 1 sample is gathered before treatment in 12 to 24 hours, and is gathered within 5 to 8 days after treating
One sample, a sample is gathered again within 12 to 20 days after treatment.
According in some embodiments, treatment refers to any as known in the art and following for glioma
Treatment, including but not limited to invasive treatment, non-invasive therapy；Including but not limited to：Chemotherapy, radiation-therapy, physical removal, life
Thing immunotherapy, Chinese medical and herbal therapy.In a specific embodiment, treatment refers to physical removal.Technical staff should
Understand, in the disclosure, the relevance between protein expression level and final therapeutic effect, not because of specific treatment method by
To influence.It means which kind for the treatment of method no matter taken, the expression of protein marker can be used for commenting in the disclosure
How is the effect of valency treatment.
In some embodiments, how effect refers to cure.
In the disclosure, healing is presented as selected from following any one or combination：Tumor resection is clean, head nuclear-magnetism is without exception
Signal, limb activity freely, no headache, without vomiting, without blurring of vision, without aphasia.
In a particular embodiment, before compared to treatment, the expression water of following albumen is selected from after treatment in subject
Pancake is low, indicates that subject's glioma is cured：N- N-acetylmuramyls-ALANINE amidase, interleukin-1 receptor antagonism
Albumen, collagen α -1 (IV) chain, ribonuclease inhibitor, thrombospondin -4, fine albumen -1 and its group
Close.In a particular embodiment, before compared to treatment, the expression of following albumen reduces in subject after treatment, instruction
Subject's glioma is cured：N- N-acetylmuramyls-ALANINE amidase, interleukin-1 receptor antagonist protein, collagen α -1
(IV) combination of chain, ribonuclease inhibitor, thrombospondin -4 and fine albumen -1.
In a particular embodiment, before compared to treatment, the expression selected from following albumen is raised and referred to after treatment
Show that subject's glioma is cured：α-crystal proteins B chains, beta-glucuronic acid, CD276 antigens, c-type Lectin domain man
The component G of race 4, gamma-Glutamyl hydrolase, Napsin-A, carcinomebryonic antigen relevant cell adhesion molecule 1, Aminopeptidase N, visible peristalsis visible intestinal peristalsis malt
Sugar-glucoamylase, the part 2 of apoptosis albumen 1, dipeptidyl peptidase 1, dihydropteridine reductase, glutamy amino
It is peptase, cystatin-C, polymerization immunoglobulin receptor, desmin -2, similar serine carboxypeptidase CPVL, annexin A7, viscous
Attached g protein coupled receptor F5, lysosome Pro-X carboxypeptidases, lysosomal associated membrane glycoprotein 1, lysosomal associated membrane glycoprotein 2,
Acid ceramidase, mitochondria 10kDa heat shock proteins, malate dehydrogenase,mitochondrial, selenium Binding Protein 1, histone
Enzyme D, p75TNFR, and combinations thereof.
Indentifying substance suitable for the disclosure is Mass Spectrometric Identification reagent, antibody or its antigen-binding fragment, probe or primer.
In a particular embodiment, antibody is monoclonal antibody.The disclosure is not limited the source of species of monoclonal antibody, any
The antibody of above-mentioned albumen, which can be combined, can use.
In a particular embodiment, antigen-binding fragment includes but is not limited to：Fab、Fab'、(Fab')2、Fv、ScFv、
Bispecific antibody, three specific antibodies, four specific antibodies, double-scFv, mimi antibody.It is any to remain the anti-of antigen-binding activity
Body fragment is applied to the disclosure.
In the technical scheme of the disclosure, the glioma is selected from：Limitation glioma or diffusivity glioma.According to
WHO central nerve neuromas are classified (2007, fourth edition), and diffusivity glioma can be divided into II, III and IV grade, including hair
Cellular type astrocytoma (WHOI levels), study of pleomorphic xanthoastrocytoma (II grade of WHO), diffusivity astrocytoma
(II grade of WHO), oligodendroglioma (II grade of WHO), dash forward astrocytoma (WHO II), human anaplastic astrocytoma (WHO less
II grade), denaturation oligodendroglioma (III grade of WHO), denaturation less dash forward astrocytoma (III grade of WHO), glioblast
Knurl (IV grade of WHO).
In a particular embodiment, diagnosis and/or prognosis glioma can be used according to the protein marker of the disclosure.
In other embodiments, therapeutic effect of the evaluation to glioma can be used according to the protein marker of the disclosure.
In a particular embodiment, expression is selected from nucleic acid level and protein level, especially protein level.
In a particular embodiment, expression determines in urine specimen.
According to another embodiment, additionally provide a kind of for diagnosis and/or prognosis glioma or for evaluating to brain
The kit or chip of the therapeutic effect of glioma, it is comprising the indentifying substance selected from following albumen or by selected from following
Albumen indentifying substance composition：α-crystal proteins B chains, beta-glucuronic acid, CD276 antigens, c-type Lectin domain family
4 component G, gamma-Glutamyl hydrolase, N- N-acetylmuramyls-ALANINE amidase, Napsin-A, carcinomebryonic antigen relevant cell
Adhesion molecule 1, Aminopeptidase N, interleukin-1 receptor antagonist protein, visible peristalsis visible intestinal peristalsis maltose-glucoamylase, apoptosis egg
White 1 part 2, dipeptidyl peptidase 1, dihydropteridine reductase, glutamy aminopeptidase, cystatin-C, ribonucleic acid enzyme level because
It is son, collagen α -1 (IV), polymerization immunoglobulin receptor, desmin -2, similar serine carboxypeptidase CPVL, annexin A7, viscous
Attached g protein coupled receptor F5, lysosome Pro-X carboxypeptidases, lysosomal associated membrane glycoprotein 1, lysosomal associated membrane glycoprotein 2,
Acid ceramidase, fine albumen -1, mitochondria 10kDa heat shock proteins, malate dehydrogenase,mitochondrial, selenium Binding Protein 1,
Thrombospondin -4, cathepsin D, p75TNFR, and combinations thereof.
In some embodiments, the indentifying substance of above-mentioned albumen is included in kit.In other embodiments, core
The indentifying substance of above-mentioned albumen is fixed with piece.In some embodiments, the indentifying substance is antibody or its antigen binding
Fragment.
According to some, embodiment there is provided a kind of method for evaluating subject's therapeutic effect on glioma, including step
Suddenly：
1) urine specimen before acquisition subject and after treatment,
2) optionally, the protein isolate from urine specimen,
3) expression selected from following albumen in the urine specimen of the subject is determined：α-crystal proteins B chains, β-
Glucuronic acid, CD276 antigens, the component G of c-type Lectin domain family 4, gamma-Glutamyl hydrolase, N- N-acetylmuramyls-
ALANINE amidase, Napsin-A, carcinomebryonic antigen relevant cell adhesion molecule 1, Aminopeptidase N, interleukin-1 receptor antagonism egg
In vain, visible peristalsis visible intestinal peristalsis maltose-glucoamylase, the part 2 of apoptosis albumen 1, dipeptidyl peptidase 1, dihydropteridine reductase,
Glutamy aminopeptidase, cystatin-C, ribonuclease inhibitor, collagen α -1 (IV), polymerization immunoglobulin receptor, knot
Close element -2, similar serine carboxypeptidase CPVL, annexin A7, attachment G protein coupled receptor F5, lysosome Pro-X carboxypeptidases,
Lysosomal associated membrane glycoprotein 1, lysosomal associated membrane glycoprotein 2, acid ceramidase, fine albumen -1, mitochondria 10kDa heat
It is shock protein, malate dehydrogenase,mitochondrial, selenium Binding Protein 1, thrombospondin -4, cathepsin D, swollen
Tumor necrosis factor receptor superfamily member 1B, and combinations thereof.
In a particular embodiment, expression is determined using mass spectrometry method, ELISA method or Western methods.
, can be with after the step of obtaining urine specimen when determining albumen and its expression using mass spectrometry method
Including digestion step.In a particular embodiment, the albumen in urine specimen is digested with protease (such as trypsase).
According to some, embodiment there is provided a kind of method for evaluating subject's therapeutic effect on glioma, including step
Suddenly：
1) urine specimen before acquisition subject and after treatment,
2) expression selected from following albumen in subject's urine specimen is determined：α-crystal proteins B chains, β-glucose
Aldehydic acid, CD276 antigens, the component G of c-type Lectin domain family 4, gamma-Glutamyl hydrolase, N- N-acetylmuramyls the third ammonia of-L-
Sour amidase, Napsin-A, carcinomebryonic antigen relevant cell adhesion molecule 1, Aminopeptidase N, interleukin-1 receptor antagonist protein, visible peristalsis visible intestinal peristalsis
Maltose-glucoamylase, the part 2 of apoptosis albumen 1, dipeptidyl peptidase 1, dihydropteridine reductase, glutamy
Aminopeptidase, cystatin-C, ribonuclease inhibitor, collagen α -1 (IV), polymerization immunoglobulin receptor, desmin -2,
Similar serine carboxypeptidase CPVL, annexin A7, attachment G protein coupled receptor F5, lysosome Pro-X carboxypeptidases, lysosome
Associated membrane glycoprotein 1, lysosomal associated membrane glycoprotein 2, acid ceramidase, fine albumen -1, mitochondria 10kDa heat shock proteins
In vain, malate dehydrogenase,mitochondrial, selenium Binding Protein 1, thrombospondin -4, cathepsin D, neoplasm necrosis
Factor acceptor superfamily member 1B, and combinations thereof
3) by the table of albumen described in the expression of albumen described in the sample after subject and the sample before treatment
It is compared up to level,
4) therapeutic effect of the glioma of the subject is determined.
In a particular embodiment, before compared to treatment, the expression water of following albumen is selected from after treatment in subject
The low instruction subject's glioma of pancake is cured：N- N-acetylmuramyls-ALANINE amidase, interleukin-1 receptor antagonism egg
In vain, collagen α -1 (IV) chain, ribonuclease inhibitor, thrombospondin -4, fine albumen -1 and combinations thereof.
In a particular embodiment, before compared to treatment, the expression selected from following albumen is raised and referred to after treatment
Show that subject's glioma is cured：α-crystal proteins B chains, beta-glucuronic acid, CD276 antigens, c-type Lectin domain man
The component G of race 4, gamma-Glutamyl hydrolase, Napsin-A, carcinomebryonic antigen relevant cell adhesion molecule 1, Aminopeptidase N, visible peristalsis visible intestinal peristalsis malt
Sugar-glucoamylase, the part 2 of apoptosis albumen 1, dipeptidyl peptidase 1, dihydropteridine reductase, glutamy amino
It is peptase, cystatin-C, polymerization immunoglobulin receptor, desmin -2, similar serine carboxypeptidase CPVL, annexin A7, viscous
Attached g protein coupled receptor F5, lysosome Pro-X carboxypeptidases, lysosomal associated membrane glycoprotein 1, lysosomal associated membrane glycoprotein 2,
Acid ceramidase, mitochondria 10kDa heat shock proteins, malate dehydrogenase,mitochondrial, selenium Binding Protein 1, histone
Enzyme D, p75TNFR, and combinations thereof.
Brief description of the drawings
Figure 1A to 1D：Patients with gliomas perioperatively brain MRI.Figure 1A and 1B：Operation consent；Fig. 1 C and 1D：Post operation.
Fig. 2：Patients with gliomas pathological examination.
Embodiment
The disclosure will be further illustrated by following non-limiting examples below.It is as well known to those skilled in the art, not
In the case of disclosure spirit, many modifications can be made to the disclosure, such modification also falls into the scope of the present disclosure.
Unless otherwise instructed, used experiment material can obtain from commercial company.
Embodiment
The collection and analysis of the patients with gliomas of embodiment 1. perioperatively urine
1. obtaining the urina sanguinis sample before patients with gliomas is preoperative and post-operative recovery is left hospital for two weeks of row tumorectomy, pass through
The comparison of preoperative and postoperative Urine in Patients protein groups, the observation preoperative illness of patient normally changes with post-operative recovery, to clinically sentencing
Disconnected After gliomas operation Cure has important directive significance.
2. material and reagent
(1) instrument：
The three-in-one mass spectrographs of Orbitrap Fusion Lumos are purchased from Thermo Fisher companies；
High performance liquid chromatograph EASY-nLC 1200 is purchased from Thermo Fisher companies.
(2) main agents：
Chromatographic grade acetonitrile, formic acid and methanol produce for Fisher companies；Iodacetyl ammonium (IAA), ammonium hydrogen carbonate, two sulphur threoses
Alcohol (DTT) is bought from Sigma companies；Mass spectrum level pancreatin is bought from Promega companies.
3. experimental method
(1) sample collects flow：Before patients with gliomas tumor resection, imageological examination is carried out to cranium, collected
The urine of pre-operative patients.Image check is carried out after corrective surgery before rehabilitation discharge in 1-2 weeks confirm that tumor resection is clean simultaneously, and
Collect the postoperative urine sample of patient.
(2) Urine in Patients albumen is extracted：Urine in Patients 5000g centrifugations 30min takes supernatant, and urine and absolute ethyl alcohol are pressed into body
Product ratio 1:3 are mixed, -20 DEG C of overnight precipitation urine albumen.4 DEG C centrifuge 30min with 12000g, abandon supernatant, precipitate natural wind
After dry plus lysate redissolves.
(3) protein groups sample preparation：Urine proteins carry out digestion on film, referring to Wisniewski JR, Zougman A,
Nagaraj N,Mann M.Universal sample preparation method for proteome
analysis.Nature methods 2009；6:359-62.
(4) Mass Spectrometric Identification：Series connection matter is carried out with Orbitrap Fusion Lumos three-in-one mass spectrographs to the peptide fragment of digestion
Spectrum analysis.With highly sensitive pattern acquiring mass spectrometric data：Two level spectrogram full scan is carried out using highest fast mode within (3 seconds),
The resolution ratio that two level scans in Orbitrap is 30000, is collided with 30% HCD energy, and screening charge number is+2 to+7
Parent ion, dynamic exclude the time be 30 seconds.
(5) protein groups quantitative analysis：Mass spectral results carry out database retrieval with mascot softwares (version 2 .5.1).It is used
Database is SwissProt_Human (08/2013).Search condition is：Pancreatin digestion；Allow there are 2 leakage enzyme sites；Half Guang ammonia
Acid+57Da fixed modification；Variable modification：Oxidation(M).Mass spectrometric data retrieves admissible error：Parent ion 10ppm, son
Ion 0.05Da.The result of database retrieval carries out proteomic data quantitative analysis by Scaffold softwares (edition 4 .4.0),
Protein level sets FDR<1%, peptide level set at least two uniqueness polypeptide be used for it is quantitative.By preoperative and postoperative protein groups
Data carry out statistical analysis, screen for preoperative compared with spectrogram number change multiple more than 1.5 times, p value less than 0.05 egg
It is used as differential protein in vain.
Test case
The head nuclear-magnetism inspection of test case 1.
Swollen thing size and location are determined by nuclear-magnetism inspection before corrective surgery, Post operation binding of pathological makes a definite diagnosis glioma；Suffer from
Check nuclear-magnetism confirms that Tumor resection is clean before the discharge in 1-2 weeks of person's post-operative rehabilitation.Before surgery and postoperative rehabilitation discharge is preceding to suffering from
Person's head carries out magnetic resonance MRI inspections, it is found that Post operation tumor tissues are removed clean (Figure 1A to 1D).
The histopathological examination of test case 2.
The tumor sample of patients with gliomas surgery excision carries out HE dyeing pathologic findings and the common molecular marker of glioma
SABC inspection, confirm that glioma is ill and WHO classification.
HE dyeing is carried out to the lump that Post operation is extractd, finds tumour cell dense arrangement, it is seen that multinuclear oncocyte, core point
Split as being clear to (Fig. 2).
The Identification of Fusion Protein of test case 3.
Collect 5 patients with gliomas (glioblastoma and oligodendroglioma) made a definite diagnosis perioperatively totally 10 urine
Liquid sample, in Identification of Fusion Protein FDR<1% level, albumen number 1422 is identified altogether.
Operation consent and the sample in the week of Post operation 1 to 2 compare, and filter out change multiple more than 1.5 times and matched samples t is examined
Test p<0.05 differential protein.
Table 1 is shown, filters out differential protein 34 altogether afterwards before surgery, and postoperative 6 albumen reduces, postoperative 28 albumen liters
It is high.Protein I D is the numbering in SwissProt.
The patients with gliomas of table 1. perioperatively difference urine protein mark
Claims (6)
1. purposes of the indentifying substance in the reagent for preparing the glioma treatment effect for being used for monitoring subject, wherein the mirror
Reagent is determined for being selected from following albumen：
α-crystal proteins B chains, beta-glucuronic acid, CD276 antigens, the component G of c-type Lectin domain family 4, gamma-glutamyl
Hydrolase, N- N-acetylmuramyls-ALANINE amidase, Napsin-A, carcinomebryonic antigen relevant cell adhesion molecule 1, aminopeptidase
N, interleukin-1 receptor antagonist protein, visible peristalsis visible intestinal peristalsis maltose-glucoamylase, the part 2 of apoptosis albumen 1, two peptidyls
Peptase 1, dihydropteridine reductase, glutamy aminopeptidase, cystatin-C, ribonuclease inhibitor, collagen α -1 (IV),
It polymerize immunoglobulin receptor, desmin -2, similar serine carboxypeptidase CPVL, annexin A7, attachment G protein coupled receptor
F5, lysosome Pro-X carboxypeptidases, lysosomal associated membrane glycoprotein 1, lysosomal associated membrane glycoprotein 2, acid ceramidase,
Fine albumen -1, mitochondria 10kDa heat shock proteins, malate dehydrogenase,mitochondrial, selenium Binding Protein 1, platelet thrombin are quick
Feel protein-4, cathepsin D, p75TNFR, and combinations thereof.
2. purposes according to claim 1, wherein：
The indentifying substance is Mass Spectrometric Identification reagent, antibody or its antigen-binding fragment, probe, primer, and preferably described antibody is
Monoclonal antibody.
3. purposes according to claim 1, wherein：
The expression selected from following albumen, which reduces, before treatment, after treatment indicates that subject's glioma is controlled
More：N- N-acetylmuramyls-ALANINE amidase, interleukin-1 receptor antagonist protein, collagen α -1 (IV) chain, ribalgilase
Inhibiting factor, thrombospondin -4, fine albumen -1 and combinations thereof；It is it is preferred that quick including at least platelet thrombin
Feel protein-4, collagen α -1 (IV) chain；Most preferably, including at least thrombospondin -4；
Before treatment, expression rise instruction subject's glioma selected from following albumen controls after treatment
More：α-crystal proteins B chains, beta-glucuronic acid, CD276 antigens, the component G of c-type Lectin domain family 4, gamma-glutamyl water
Solve enzyme, Napsin-A, carcinomebryonic antigen relevant cell adhesion molecule 1, Aminopeptidase N, visible peristalsis visible intestinal peristalsis maltose-glucoamylase, procedural
The part 2 of cell death albumen 1, dipeptidyl peptidase 1, dihydropteridine reductase, glutamy aminopeptidase, cystatin-C, polymerization are exempted from
It is epidemic disease Ig receptor, desmin -2, similar serine carboxypeptidase CPVL, annexin A7, attachment G protein coupled receptor F5, molten
Enzyme body Pro-X carboxypeptidases, lysosomal associated membrane glycoprotein 1, lysosomal associated membrane glycoprotein 2, acid ceramidase, mitochondria
10kDa heat shock proteins, malate dehydrogenase,mitochondrial, selenium Binding Protein 1, cathepsin D, Tumor Necrosis Factor Receptors surpass
Family member 1B, and combinations thereof；Preferably at least include：Annexin A7, attachment G protein coupled receptor F5, mitochondria 10kDa heat
Shock protein or carcinomebryonic antigen relevant cell adhesion molecule 1；Most preferably at least include carcinomebryonic antigen relevant cell adhesion molecule 1；
Refer to before treatment, receive 0 to 72 hour a few days ago for the treatment of in the subject；
Refer to after treatment, 5 to 20 days, preferably 6 to 15 days, more preferably 7 to 14 days after the subject receives the day for the treatment of.
4. purposes according to claim 3, wherein described expression refers in subject's urine specimen
Expression.
5. purposes according to any one of claim 1 to 4, wherein the glioma is selected from：Limitation glioma, more
Unrestrained property glioma；
Wherein described diffusivity glioma is selected from：Pilocytic Astrocytoma, study of pleomorphic xanthoastrocytoma, more
Unrestrained property astrocytoma, oligodendroglioma, astrocytoma of dashing forward less, human anaplastic astrocytoma, a denaturation oligodendroglia
Cytoma, denaturation less dash forward astrocytoma, glioblastoma, and combinations thereof；It is preferred that glioblastoma, oligodendroglia
Cytoma.
6. a kind of kit or chip for being used to monitor glioma treatment effect, it, which is included, is directed to the mirror selected from following albumen
Determine reagent：
α-crystal proteins B chains, beta-glucuronic acid, CD276 antigens, the component G of c-type Lectin domain family 4, gamma-glutamyl
Hydrolase, N- N-acetylmuramyls-ALANINE amidase, Napsin-A, carcinomebryonic antigen relevant cell adhesion molecule 1, aminopeptidase
N, interleukin-1 receptor antagonist protein, visible peristalsis visible intestinal peristalsis maltose-glucoamylase, the part 2 of apoptosis albumen 1, two peptidyls
Peptase 1, dihydropteridine reductase, glutamy aminopeptidase, cystatin-C, ribonuclease inhibitor, polymerization immune globulin
Polymeric immunoglobulin receptor, desmin -2, collagen α -1 (IV) chain, similar serine carboxypeptidase CPVL, annexin A7, attachment G protein coupling by
Body F5, lysosome Pro-X carboxypeptidases, lysosomal associated membrane glycoprotein 1, lysosomal associated membrane glycoprotein 2, acid ceramide
Enzyme, fine albumen -1, mitochondria 10kDa heat shock proteins, malate dehydrogenase,mitochondrial, selenium Binding Protein 1, platelet thrombin
Sensitive Protein -4, cathepsin D, p75TNFR, and combinations thereof；
The indentifying substance is Mass Spectrometric Identification reagent, antibody or its antigen-binding fragment, probe, primer, and preferably described antibody is
Monoclonal antibody.
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| CN108704123A (en) * | 2018-08-03 | 2018-10-26 | 辽宁师范大学 | Applications of the rLm-cystatin F in preparing anticol matter tumor medicine |
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| CN109825587A (en) * | 2019-03-14 | 2019-05-31 | 皖南医学院第一附属医院（皖南医学院弋矶山医院） | A kind of glioma prognostic marker CPVL and its application |
| CN109929844A (en) * | 2019-03-14 | 2019-06-25 | 皖南医学院第一附属医院（皖南医学院弋矶山医院） | A kind of glioma prognostic marker CPVL inhibitor and its application |
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| CN108704123B (en) * | 2018-08-03 | 2021-11-19 | 辽宁师范大学 | Application of rLm-cystatin F in preparation of anti-glioma drug |
| CN109444277A (en) * | 2018-10-29 | 2019-03-08 | 郑州大学第附属医院 | Application of the metabolic markers in terms of preparing diagnosis of glioma kit |
| CN109444277B (en) * | 2018-10-29 | 2021-05-11 | 郑州大学第一附属医院 | Application of metabolic marker in preparation of glioma diagnostic kit |
| CN109825587A (en) * | 2019-03-14 | 2019-05-31 | 皖南医学院第一附属医院（皖南医学院弋矶山医院） | A kind of glioma prognostic marker CPVL and its application |
| CN109929844A (en) * | 2019-03-14 | 2019-06-25 | 皖南医学院第一附属医院（皖南医学院弋矶山医院） | A kind of glioma prognostic marker CPVL inhibitor and its application |
| CN109825587B (en) * | 2019-03-14 | 2022-04-08 | 皖南医学院第一附属医院（皖南医学院弋矶山医院） | Glioma prognostic marker CPVL and application thereof |
| CN110568194A (en) * | 2019-09-03 | 2019-12-13 | 首都医科大学附属北京天坛医院 | Protein marker of urine low-grade glioma and application of protein marker in early diagnosis |
| CN110568196A (en) * | 2019-09-11 | 2019-12-13 | 中国医学科学院基础医学研究所 | Metabolic marker related to low-grade glioma in urine and application thereof |
| CN110632231A (en) * | 2019-10-12 | 2019-12-31 | 首都医科大学附属北京天坛医院 | Metabolic marker of glioblastoma in urine and use thereof in early diagnosis |
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