CN117110617A - 一组与慢阻肺频繁急性加重表型相关的标志物及其应用 - Google Patents
一组与慢阻肺频繁急性加重表型相关的标志物及其应用 Download PDFInfo
- Publication number
- CN117110617A CN117110617A CN202310784687.1A CN202310784687A CN117110617A CN 117110617 A CN117110617 A CN 117110617A CN 202310784687 A CN202310784687 A CN 202310784687A CN 117110617 A CN117110617 A CN 117110617A
- Authority
- CN
- China
- Prior art keywords
- phenotype
- acute exacerbation
- obstructive pulmonary
- slow
- frequent
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 230000009798 acute exacerbation Effects 0.000 title claims abstract description 99
- 230000001684 chronic effect Effects 0.000 title claims description 20
- 230000002685 pulmonary effect Effects 0.000 title claims description 19
- 230000000414 obstructive effect Effects 0.000 title claims description 16
- 102000004169 proteins and genes Human genes 0.000 claims abstract description 36
- 235000018102 proteins Nutrition 0.000 claims abstract description 34
- 239000003550 marker Substances 0.000 claims abstract description 20
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims abstract description 14
- 108010015720 Dopamine beta-Hydroxylase Proteins 0.000 claims abstract description 8
- 102100033156 Dopamine beta-hydroxylase Human genes 0.000 claims abstract description 8
- 102000001155 apolipoprotein F Human genes 0.000 claims abstract description 8
- 108010069427 apolipoprotein F Proteins 0.000 claims abstract description 8
- 102100027300 Extracellular serine/threonine protein kinase FAM20C Human genes 0.000 claims abstract description 7
- 101000937709 Homo sapiens Extracellular serine/threonine protein kinase FAM20C Proteins 0.000 claims abstract description 7
- 230000001926 lymphatic effect Effects 0.000 claims abstract description 7
- 108010008184 Aryldialkylphosphatase Proteins 0.000 claims abstract description 6
- 101001024441 Candida albicans (strain SC5314 / ATCC MYA-2876) Major facilitator superfamily multidrug transporter NAG3 Proteins 0.000 claims abstract description 6
- 101001054921 Homo sapiens Lymphatic vessel endothelial hyaluronic acid receptor 1 Proteins 0.000 claims abstract description 6
- 101000662690 Homo sapiens Trafficking protein particle complex subunit 10 Proteins 0.000 claims abstract description 6
- 108060003951 Immunoglobulin Proteins 0.000 claims abstract description 6
- 102100026849 Lymphatic vessel endothelial hyaluronic acid receptor 1 Human genes 0.000 claims abstract description 6
- 102100037456 Trafficking protein particle complex subunit 10 Human genes 0.000 claims abstract description 6
- UQHKFADEQIVWID-UHFFFAOYSA-N cytokinin Natural products C1=NC=2C(NCC=C(CO)C)=NC=NC=2N1C1CC(O)C(CO)O1 UQHKFADEQIVWID-UHFFFAOYSA-N 0.000 claims abstract description 6
- 239000004062 cytokinin Substances 0.000 claims abstract description 6
- 230000003511 endothelial effect Effects 0.000 claims abstract description 6
- 102000018358 immunoglobulin Human genes 0.000 claims abstract description 6
- 230000037361 pathway Effects 0.000 claims abstract description 6
- 230000003248 secreting effect Effects 0.000 claims abstract description 6
- 108010059343 MM Form Creatine Kinase Proteins 0.000 claims abstract description 5
- 229940122618 Trypsin inhibitor Drugs 0.000 claims abstract description 5
- 238000003860 storage Methods 0.000 claims abstract description 5
- 239000002753 trypsin inhibitor Substances 0.000 claims abstract description 5
- 102000006996 Aryldialkylphosphatase Human genes 0.000 claims abstract 2
- 108090000623 proteins and genes Proteins 0.000 claims description 35
- 210000004072 lung Anatomy 0.000 claims description 24
- 238000001514 detection method Methods 0.000 claims description 17
- 238000000034 method Methods 0.000 claims description 13
- 108700025647 major vault Proteins 0.000 claims description 12
- 238000004458 analytical method Methods 0.000 claims description 8
- 108010033918 Alanine-glyoxylate transaminase Proteins 0.000 claims description 7
- 230000000694 effects Effects 0.000 claims description 7
- 210000004369 blood Anatomy 0.000 claims description 6
- 239000008280 blood Substances 0.000 claims description 6
- 210000001124 body fluid Anatomy 0.000 claims description 6
- 239000010839 body fluid Substances 0.000 claims description 6
- 239000003814 drug Substances 0.000 claims description 6
- 208000011623 Obstructive Lung disease Diseases 0.000 claims description 5
- 238000011156 evaluation Methods 0.000 claims description 5
- 238000012216 screening Methods 0.000 claims description 5
- 239000000126 substance Substances 0.000 claims description 5
- 238000002965 ELISA Methods 0.000 claims description 4
- 102100026842 Serine-pyruvate aminotransferase Human genes 0.000 claims description 4
- 229940079593 drug Drugs 0.000 claims description 4
- 238000007477 logistic regression Methods 0.000 claims description 4
- 108010060800 serine-pyruvate aminotransferase Proteins 0.000 claims description 4
- 238000006243 chemical reaction Methods 0.000 claims description 3
- 239000003153 chemical reaction reagent Substances 0.000 claims description 3
- 238000004949 mass spectrometry Methods 0.000 claims description 3
- 230000002093 peripheral effect Effects 0.000 claims description 3
- 206010036790 Productive cough Diseases 0.000 claims description 2
- 102000001253 Protein Kinase Human genes 0.000 claims description 2
- 238000003556 assay Methods 0.000 claims description 2
- 238000004364 calculation method Methods 0.000 claims description 2
- 239000012530 fluid Substances 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 108060006633 protein kinase Proteins 0.000 claims description 2
- 210000003296 saliva Anatomy 0.000 claims description 2
- 210000003802 sputum Anatomy 0.000 claims description 2
- 208000024794 sputum Diseases 0.000 claims description 2
- 210000004243 sweat Anatomy 0.000 claims description 2
- 210000002700 urine Anatomy 0.000 claims description 2
- 108091000080 Phosphotransferase Proteins 0.000 abstract description 5
- 102000020233 phosphotransferase Human genes 0.000 abstract description 5
- 239000000090 biomarker Substances 0.000 abstract description 4
- 108091005461 Nucleic proteins Proteins 0.000 abstract description 3
- HHLFWLYXYJOTON-UHFFFAOYSA-N glyoxylic acid Chemical compound OC(=O)C=O HHLFWLYXYJOTON-UHFFFAOYSA-N 0.000 abstract description 3
- 108020004707 nucleic acids Proteins 0.000 abstract description 3
- 102000039446 nucleic acids Human genes 0.000 abstract description 3
- 150000007523 nucleic acids Chemical class 0.000 abstract description 3
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 abstract 1
- 102000003929 Transaminases Human genes 0.000 abstract 1
- 108090000340 Transaminases Proteins 0.000 abstract 1
- 235000004279 alanine Nutrition 0.000 abstract 1
- 208000019693 Lung disease Diseases 0.000 description 8
- 239000007788 liquid Substances 0.000 description 7
- 102100035476 Serum paraoxonase/arylesterase 1 Human genes 0.000 description 6
- 238000010201 enrichment analysis Methods 0.000 description 6
- 230000035945 sensitivity Effects 0.000 description 6
- 238000005406 washing Methods 0.000 description 5
- 230000001154 acute effect Effects 0.000 description 4
- 238000013211 curve analysis Methods 0.000 description 4
- 239000011148 porous material Substances 0.000 description 4
- 238000007789 sealing Methods 0.000 description 4
- 230000000391 smoking effect Effects 0.000 description 4
- 238000003745 diagnosis Methods 0.000 description 3
- 238000003748 differential diagnosis Methods 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 230000019491 signal transduction Effects 0.000 description 3
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 description 2
- 108010017384 Blood Proteins Proteins 0.000 description 2
- 102000004506 Blood Proteins Human genes 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 2
- 102100039460 Inter-alpha-trypsin inhibitor heavy chain H3 Human genes 0.000 description 2
- 102000017500 Septin 2 Human genes 0.000 description 2
- 108050005721 Septin 2 Proteins 0.000 description 2
- 108010090804 Streptavidin Proteins 0.000 description 2
- 239000002250 absorbent Substances 0.000 description 2
- 230000002745 absorbent Effects 0.000 description 2
- 238000010009 beating Methods 0.000 description 2
- 239000002551 biofuel Substances 0.000 description 2
- 230000001413 cellular effect Effects 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 2
- 238000013399 early diagnosis Methods 0.000 description 2
- 230000006870 function Effects 0.000 description 2
- 229920002674 hyaluronan Polymers 0.000 description 2
- 229960003160 hyaluronic acid Drugs 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 238000004393 prognosis Methods 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 230000003595 spectral effect Effects 0.000 description 2
- 230000032258 transport Effects 0.000 description 2
- SFLSHLFXELFNJZ-QMMMGPOBSA-N (-)-norepinephrine Chemical compound NC[C@H](O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-QMMMGPOBSA-N 0.000 description 1
- WIVGIKIKQHUFOD-UHFFFAOYSA-N 4-fluoro-n-methyl-n-[4-[6-(propan-2-ylamino)pyrimidin-4-yl]-1,3-thiazol-2-yl]benzamide Chemical compound C1=NC(NC(C)C)=CC(C=2N=C(SC=2)N(C)C(=O)C=2C=CC(F)=CC=2)=N1 WIVGIKIKQHUFOD-UHFFFAOYSA-N 0.000 description 1
- 102000007469 Actins Human genes 0.000 description 1
- 108010085238 Actins Proteins 0.000 description 1
- 102100032156 Adenylate cyclase type 9 Human genes 0.000 description 1
- 102100022524 Alpha-1-antichymotrypsin Human genes 0.000 description 1
- 102100022014 Angiopoietin-1 receptor Human genes 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- 108091006146 Channels Proteins 0.000 description 1
- 208000017667 Chronic Disease Diseases 0.000 description 1
- 108010079245 Cystic Fibrosis Transmembrane Conductance Regulator Proteins 0.000 description 1
- 101100390778 Drosophila melanogaster Fitm2 gene Proteins 0.000 description 1
- 102100031780 Endonuclease Human genes 0.000 description 1
- 108010042407 Endonucleases Proteins 0.000 description 1
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 1
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 1
- 102100036990 Fat storage-inducing transmembrane protein 1 Human genes 0.000 description 1
- 102100027842 Fibroblast growth factor receptor 3 Human genes 0.000 description 1
- 101710182396 Fibroblast growth factor receptor 3 Proteins 0.000 description 1
- 101000775499 Homo sapiens Adenylate cyclase type 9 Proteins 0.000 description 1
- 101000678026 Homo sapiens Alpha-1-antichymotrypsin Proteins 0.000 description 1
- 101000753291 Homo sapiens Angiopoietin-1 receptor Proteins 0.000 description 1
- 101000576898 Homo sapiens C-type mannose receptor 2 Proteins 0.000 description 1
- 101000878236 Homo sapiens Fat storage-inducing transmembrane protein 1 Proteins 0.000 description 1
- 101000975428 Homo sapiens Inositol 1,4,5-trisphosphate receptor type 1 Proteins 0.000 description 1
- 101001078143 Homo sapiens Integrin alpha-IIb Proteins 0.000 description 1
- 101000976697 Homo sapiens Inter-alpha-trypsin inhibitor heavy chain H1 Proteins 0.000 description 1
- 101000609406 Homo sapiens Inter-alpha-trypsin inhibitor heavy chain H3 Proteins 0.000 description 1
- 101000605403 Homo sapiens Plasminogen Proteins 0.000 description 1
- 101001067178 Homo sapiens Plexin-A4 Proteins 0.000 description 1
- 101000669917 Homo sapiens Rho-associated protein kinase 1 Proteins 0.000 description 1
- 101000869480 Homo sapiens Serum amyloid A-1 protein Proteins 0.000 description 1
- 101001094647 Homo sapiens Serum paraoxonase/arylesterase 1 Proteins 0.000 description 1
- 101000881267 Homo sapiens Spectrin alpha chain, erythrocytic 1 Proteins 0.000 description 1
- 101000704198 Homo sapiens Spectrin beta chain, non-erythrocytic 2 Proteins 0.000 description 1
- 101001050476 Homo sapiens Tyrosine-protein kinase ITK/TSK Proteins 0.000 description 1
- 101000807541 Homo sapiens Ubiquitin carboxyl-terminal hydrolase 24 Proteins 0.000 description 1
- 102000018866 Hyaluronan Receptors Human genes 0.000 description 1
- 108010013214 Hyaluronan Receptors Proteins 0.000 description 1
- 206010021143 Hypoxia Diseases 0.000 description 1
- 102100024039 Inositol 1,4,5-trisphosphate receptor type 1 Human genes 0.000 description 1
- 102100025306 Integrin alpha-IIb Human genes 0.000 description 1
- 102100023490 Inter-alpha-trypsin inhibitor heavy chain H1 Human genes 0.000 description 1
- 101710083925 Inter-alpha-trypsin inhibitor heavy chain H3 Proteins 0.000 description 1
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- 102100022743 Laminin subunit alpha-4 Human genes 0.000 description 1
- 102100034069 MAP kinase-activated protein kinase 2 Human genes 0.000 description 1
- 108010041955 MAP-kinase-activated kinase 2 Proteins 0.000 description 1
- 102000009571 Macrophage Inflammatory Proteins Human genes 0.000 description 1
- 108010009474 Macrophage Inflammatory Proteins Proteins 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 206010073310 Occupational exposures Diseases 0.000 description 1
- 108090000854 Oxidoreductases Proteins 0.000 description 1
- 102000004316 Oxidoreductases Human genes 0.000 description 1
- 108010033276 Peptide Fragments Proteins 0.000 description 1
- 102000007079 Peptide Fragments Human genes 0.000 description 1
- 102100038124 Plasminogen Human genes 0.000 description 1
- 108010051742 Platelet-Derived Growth Factor beta Receptor Proteins 0.000 description 1
- 102100026547 Platelet-derived growth factor receptor beta Human genes 0.000 description 1
- 102100034385 Plexin-A4 Human genes 0.000 description 1
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
- 108010026552 Proteome Proteins 0.000 description 1
- 238000001069 Raman spectroscopy Methods 0.000 description 1
- 102100039313 Rho-associated protein kinase 1 Human genes 0.000 description 1
- 102000006382 Ribonucleases Human genes 0.000 description 1
- 108010083644 Ribonucleases Proteins 0.000 description 1
- 102100032277 Serum amyloid A-1 protein Human genes 0.000 description 1
- 101710180981 Serum paraoxonase/arylesterase 1 Proteins 0.000 description 1
- 102100037608 Spectrin alpha chain, erythrocytic 1 Human genes 0.000 description 1
- 102100031864 Spectrin beta chain, non-erythrocytic 2 Human genes 0.000 description 1
- 101710172711 Structural protein Proteins 0.000 description 1
- 238000000692 Student's t-test Methods 0.000 description 1
- 102000004142 Trypsin Human genes 0.000 description 1
- 108090000631 Trypsin Proteins 0.000 description 1
- 102100023345 Tyrosine-protein kinase ITK/TSK Human genes 0.000 description 1
- 102100037176 Ubiquitin carboxyl-terminal hydrolase 24 Human genes 0.000 description 1
- 102000006668 UniProt protein families Human genes 0.000 description 1
- 108020004729 UniProt protein families Proteins 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 230000010100 anticoagulation Effects 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 230000008952 bacterial invasion Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 238000003766 bioinformatics method Methods 0.000 description 1
- 230000031018 biological processes and functions Effects 0.000 description 1
- 201000009267 bronchiectasis Diseases 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 230000021164 cell adhesion Effects 0.000 description 1
- 230000012292 cell migration Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- 238000003759 clinical diagnosis Methods 0.000 description 1
- 230000015271 coagulation Effects 0.000 description 1
- 238000005345 coagulation Methods 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 230000001054 cortical effect Effects 0.000 description 1
- 230000001086 cytosolic effect Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000001784 detoxification Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 229960003638 dopamine Drugs 0.000 description 1
- 239000002158 endotoxin Substances 0.000 description 1
- 230000019439 energy homeostasis Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000004890 epithelial barrier function Effects 0.000 description 1
- 210000002919 epithelial cell Anatomy 0.000 description 1
- 230000032050 esterification Effects 0.000 description 1
- 238000005886 esterification reaction Methods 0.000 description 1
- 230000005713 exacerbation Effects 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 210000002744 extracellular matrix Anatomy 0.000 description 1
- 210000001723 extracellular space Anatomy 0.000 description 1
- 210000002950 fibroblast Anatomy 0.000 description 1
- 238000001794 hormone therapy Methods 0.000 description 1
- 230000007954 hypoxia Effects 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 102000008371 intracellularly ATP-gated chloride channel activity proteins Human genes 0.000 description 1
- 108010008094 laminin alpha 3 Proteins 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 230000004322 lipid homeostasis Effects 0.000 description 1
- 229920006008 lipopolysaccharide Polymers 0.000 description 1
- 230000033001 locomotion Effects 0.000 description 1
- 230000004199 lung function Effects 0.000 description 1
- 230000036210 malignancy Effects 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004879 molecular function Effects 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 230000001114 myogenic effect Effects 0.000 description 1
- 210000000440 neutrophil Anatomy 0.000 description 1
- 229960002748 norepinephrine Drugs 0.000 description 1
- SFLSHLFXELFNJZ-UHFFFAOYSA-N norepinephrine Natural products NCC(O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-UHFFFAOYSA-N 0.000 description 1
- 231100000675 occupational exposure Toxicity 0.000 description 1
- 230000035778 pathophysiological process Effects 0.000 description 1
- 238000003068 pathway analysis Methods 0.000 description 1
- 210000002824 peroxisome Anatomy 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 208000005069 pulmonary fibrosis Diseases 0.000 description 1
- 230000009325 pulmonary function Effects 0.000 description 1
- 238000004445 quantitative analysis Methods 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000006798 recombination Effects 0.000 description 1
- 238000005215 recombination Methods 0.000 description 1
- 230000000306 recurrent effect Effects 0.000 description 1
- 230000000241 respiratory effect Effects 0.000 description 1
- 210000002345 respiratory system Anatomy 0.000 description 1
- 208000023504 respiratory system disease Diseases 0.000 description 1
- 238000004007 reversed phase HPLC Methods 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 210000002027 skeletal muscle Anatomy 0.000 description 1
- 238000002791 soaking Methods 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 239000012089 stop solution Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 238000012353 t test Methods 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 230000026683 transduction Effects 0.000 description 1
- 238000010361 transduction Methods 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 239000012588 trypsin Substances 0.000 description 1
- 108700026220 vif Genes Proteins 0.000 description 1
- 230000029663 wound healing Effects 0.000 description 1
Classifications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
- G01N33/6893—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids related to diseases not provided for elsewhere
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/573—Immunoassay; Biospecific binding assay; Materials therefor for enzymes or isoenzymes
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
- G01N33/6854—Immunoglobulins
- G01N33/6857—Antibody fragments
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2800/00—Detection or diagnosis of diseases
- G01N2800/12—Pulmonary diseases
- G01N2800/122—Chronic or obstructive airway disorders, e.g. asthma COPD
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Immunology (AREA)
- Molecular Biology (AREA)
- Chemical & Material Sciences (AREA)
- Biomedical Technology (AREA)
- Urology & Nephrology (AREA)
- Hematology (AREA)
- Biotechnology (AREA)
- Analytical Chemistry (AREA)
- Cell Biology (AREA)
- Pathology (AREA)
- Food Science & Technology (AREA)
- Medicinal Chemistry (AREA)
- Physics & Mathematics (AREA)
- Microbiology (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- General Physics & Mathematics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Investigating Or Analysing Biological Materials (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
Abstract
本发明公开了一组与慢性阻塞性肺病(chronicobstructivepulmonarydisease，慢阻肺)频繁急性加重表型相关的标志物及其应用。所述标志物包括间α‑胰蛋白酶抑制因子重链H3、淋巴管内皮透明质酸受体1、对氧磷酶1、丙氨酸乙醛酸转氨酶、免疫球蛋白κ可变区3D‑11、胞裂蛋白2、载脂蛋白F、多巴胺β‑羟化酶、肌肉肌酸激酶、FAM20C高尔基体相关分泌途径激酶或脂肪储存诱导跨膜蛋白1中任意一种或至少两种的组合。本发明挖掘全新的、可用于慢阻肺稳定期检出与鉴定频繁急性加重与非频繁急性加重表型患者人群的一组核酸/蛋白质生物标志物，能鉴别诊断慢阻肺两个不同表型患者人群，并进行精准治疗和早期预警。
Description
技术领域
本发明属于生物技术领域，涉及一组与慢阻肺频繁急性加重表型相关的标志物及其应用。
背景技术
慢阻肺是一种常见的、渐进性呼吸道气流受阻的重大慢性疾病。根据患者每年急性加重的发作频率，慢阻肺患者可分为两种临床表型人群，即频繁急性加重和非频繁急性加重。频繁急性加重是慢阻肺的一种预后更差的独特表型，与非频繁急性加重患者相比，呼吸道病变更重，肺功能恶化更快，住院风险更高，患者因缺氧导致的其它严重并发症，使得生活质量更差和家庭经济负荷更大。这一亚型状态意味着存在许多复杂的潜在因素，可调节慢阻肺不同亚型的病理生理过程，正是这些因素可以决定患者对慢阻肺反复急性发作的易感性，并导致慢阻肺病变的严重程度和预后转归。
目前慢阻肺频繁急性加重表型依靠临床评估，根据患者对先前治疗事件的回忆来预测，不仅耗时而且标准难以统一，尚缺少一个快速、便捷、统一、实用的诊断标准和检测手段，需要通过发现具有特异性、功能性的和简单易行、适用于临床的生物标志物来指导临床上对慢阻肺频繁急性加重患者的早期诊断、精准干预和个性化治疗，如CN114410772A公开了检测待测对象易感基因是否发生突变的物质在制备预测或辅助预测待测对象是否易感慢阻肺急性加重表型产品中的应用，所述易感基因为ITK，ROCK1，ADCY9，ITGA2B，PDGFRB，FGFR3，SERPINA3，ITPR1，CFTR，USP24，SAA1，TEK，SPTBN2，PLXNA4，SPTA1，PLG，MAPKAPK2，LAMA3，P4HB和/或MRC2基因。
综上所述，开发新型的、与慢阻肺频繁急性加重表型相关的标志物，丰富检测指标和手段，对于慢阻肺治疗领域具有重要意义。
发明内容
针对现有技术的不足和实际需求，本发明提供一组与慢阻肺频繁急性加重表型相关的标志物及其应用，挖掘新型的、高特异性和高灵敏性的核酸/蛋白质标志物，可用于检测与诊断慢阻肺频繁急性加重与非频繁急性加重患者。
为达上述目的，本发明采用以下技术方案：
第一方面，本发明提供一组与慢阻肺频繁急性加重表型相关的标志物，其特征在于，所述标志物包括间α-胰蛋白酶抑制因子重链H3(ITIH3)、淋巴管内皮透明质酸受体1(LYVE1)、对氧磷酶1(PON1)、丙氨酸乙醛酸转氨酶(AGXT)、免疫球蛋白κ可变区3D-11、胞裂蛋白2(SEPTIN2)、载脂蛋白F(APOF)、多巴胺β-羟化酶(DBH)、肌肉肌酸激酶(CKM)、FAM20C高尔基体相关分泌途径激酶(FAM20C)或脂肪储存诱导跨膜蛋白1(FITM1)中任意一种或至少两种的组合。
本发明中，间α-胰蛋白酶抑制因子重链H3，与透明质酸共价结合，对稳定细胞外基质起重要作用；淋巴管内皮透明质酸受体1，参与淋巴透明质酸的转运；对氧磷酶1，一种抗氧化酶，抑制脂多糖诱导的巨噬细胞炎性细胞因子的分泌和肺成纤维细胞的增殖；丙氨酸乙醛酸转氨酶，主要定位于过氧化物酶体，参与乙醛酸解毒；免疫球蛋白κ可变区3D-11，参与抗原识别；胞裂蛋白2，通过改变皮层肌动蛋白的表达，调节气道上皮屏障功能；载脂蛋白F，参与胆固醇的运输和/或酯化；多巴胺β-羟化酶，一种氧化还原酶，催化多巴胺向去甲肾上腺素转化；肌肉肌酸激酶，参与能量稳态的细胞质酶在能量需求波动较大的组织中，如骨骼肌的能量转导中起着重要作用；FAM20C高尔基体相关分泌途径激酶，在脂质稳态、伤口愈合和细胞迁移和粘附中发挥作用；脂肪储存诱导跨膜蛋白1参与肌肉发育。
本发明中，采用高灵敏、高通量蛋白组学检测方法，通过对慢阻肺频繁急性加重与慢阻肺非频繁急性加重两组患者血浆标本进行队列检测、统计学比较和生物信息学分析，捕获慢阻肺频繁急性加重与非频繁急性加重两组间、与各自疾病表型特征相关的血浆表达蛋白质47个。经过GO富集分析、KEGG信号通路富集分析和ROC曲线分析，又从其中挑选出11个AUC>0.7的蛋白质(包括间α-胰蛋白酶抑制因子重链H3、淋巴管内皮透明质酸受体1、对氧磷酶1、丙氨酸乙醛酸转氨酶、免疫球蛋白κ可变区3D-11、胞裂蛋白2、载脂蛋白F、多巴胺β-羟化酶、肌肉肌酸激酶、FAM20C高尔基体相关分泌途径激酶或脂肪储存诱导跨膜蛋白1)，11个差异蛋白质的ROC分析结果显示AUC为0.985(95％CI:0.966～1.000)，灵敏度为90.9％，特异性为100％。可在慢阻肺疾病稳定期用作于临床早期诊断/鉴别诊断频繁急性加重与非频繁急性加重表型患者人群的检测标志物，预警和干预慢阻肺频繁急性加重的发生，以及做好对慢阻肺频繁急性加重的预防和有效治疗。
第二方面，本发明提供如第一方面所述的与慢阻肺频繁急性加重表型相关的标志物和/或检测其的物质在制备预测或辅助预测慢阻肺频繁急性加重表型的产品中的应用。
第三方面，本发明提供一种预测或辅助预测慢阻肺频繁急性加重表型的产品，所述产品包括检测第一方面所述的与慢阻肺频繁急性加重表型相关的标志物的表达水平的试剂和/或设备。
第四方面，本发明提供如第一方面所述的与慢阻肺频繁急性加重表型相关的标志物在构建慢阻肺频繁急性加重表型预测模型或/和制备慢阻肺频繁急性加重表型预测装置中的应用。
第五方面，本发明提供一种慢阻肺频繁急性加重表型预测模型，所述预测模型用于执行包括：
输入第一方面所述的与慢阻肺频繁急性加重表型相关的标志物的表达水平，拟合二元logistic回归模型；
利用拟合的二元logistic回归模型，计算Nomogram结果，根据模型中各个蛋白质对结局变量的贡献程度，给每个蛋白质的表达水平进行赋分，然后再将各个评分相加得到总评分，最后通过总评分与结局事件发生概率之间的函数转换关系，从而计算出该患者是慢阻肺频繁急性加重表型的预测值，如图1所示。
本发明中，纳入11个筛选得到的蛋白：ITIH3+LYVE1+PON1+AGXT+IGKV3D+Septin-2+APOF+DBH+CKM+FAM20C+FITM1拟合的模型得到ROC曲线，AUC＝0.985，具有较高的诊断预测效果。
第六方面，本发明提供一种慢阻肺频繁急性加重表型预测装置，所述装置包括检测单元和评估单元。
所述检测单元用于执行包括：
检测受试者的待测体液样品中第一方面所述的与慢阻肺频繁急性加重表型相关的标志物的表达水平。
所述评估单元用于执行包括：
将分析单元检测到的与慢阻肺频繁急性加重表型相关的标志物的表达水平输入第五方面所述的慢阻肺频繁急性加重表型预测模型中进行计算，并判断是否为慢阻肺稳定期频繁急性加重患者。
优选地，所述体液待测样品包括外周循环血、尿液、唾液、痰液、灌洗液、汗液或体液胞外囊泡中任意一种。
优选地，所述检测的方法包括蛋白质谱法、酶联免疫法或蛋白芯片法。
第七方面，本发明提供第一方面所述的与慢阻肺频繁急性加重表型相关的标志物作为靶点在筛选预防或治疗慢阻肺频繁急性加重表型的药物中的应用。
优选地，所述筛选包括基于候选药物使用前和使用后对所述与慢阻肺频繁急性加重表型相关的标志物的影响，从而确定候选药物是否可以用于预防或治疗慢阻肺频繁急性加重表型。
与现有技术相比，本发明具有以下有益效果：
本发明挖掘全新的、可用于慢阻肺稳定期检出与鉴定频繁急性加重与非频繁急性加重表型两组患者人群的生物标志物，能提高检测的特异性和准确性，ROC分析结果显示AUC为0.985(95％CI:0.966～1.000)，灵敏度为90.9％，特异性为100％，能够用于临床诊断/鉴别诊断频繁急性加重与非频繁急性加重表型患者人群的检测标志物，预警和干预慢阻肺频繁急性加重的发生，以及做好对慢阻肺频繁急性加重的预防和有效治疗。
附图说明
图1为慢阻肺频繁急性加重组与非频繁急性加重组的诺曼图(列线图)，通过给每个蛋白基因的表达水平一个评分，对每个患者，就可计算得到一个总分，再通过得分与结局发生概率之间的转换函数来计算每个患者的频繁急性发生的概率；
图2为慢阻肺频繁急性加重组与非频繁急性加重组差异蛋白质火山图，FC>1.2或<0.83和p值＜0.05；
图3为慢阻肺频繁急性加重组与非频繁急性加重组差异蛋白质GO分析结果图；
图4为慢阻肺频繁急性加重组与非频繁急性加重组差异蛋白质KEEG分析结果图；
图5为预测慢阻肺频繁急性加重表型的差异蛋白质ROC曲线图；
图6为预测慢阻肺频繁急性加重表型的11个差异蛋白质联合ROC曲线图。
具体实施方式
为进一步阐述本发明所采取的技术手段及其效果，以下结合实施例和附图对本发明作进一步地说明。可以理解的是，此处所描述的具体实施方式仅仅用于解释本发明，而非对本发明的限定。
实施例中未注明具体技术或条件者，按照本领域内的文献所描述的技术或条件，或者按照产品说明书进行。所用试剂或仪器未注明生产厂商者，均为可通过正规渠道购买获得的常规产品。
实施例1
分别采集慢阻肺34例频繁急性加重患者和42例非频繁急性加重患者的血浆，然后通过高通量蛋白组学方法对慢阻肺频繁急性加重患者血浆和慢阻肺非频繁急性加重患者血浆进行比较分析。
具体过程如下：
本研究纳入2017.3～2018.9于复旦大学附属中山医院门诊就诊的慢阻肺稳定期患者(入组前4周内无急性加重病史)，根据既往急性加重史把患者分为频繁急性加重组和非频繁急性加重组。急性加重定义为呼吸道症状急性恶化，导致需要急诊或住院使用抗生素、全身激素治疗。频繁急性加重定义为每年至少发生2次急性加重或因为1次加重而导致住院治疗。研究者记录患者的人口统计学资料，吸烟史及生物燃料、职业暴露史，实验室检查，肺功能，并且采集患者的外周静脉血。所纳入的患者年龄≥40岁，并且有吸烟史(吸烟年数×每日吸烟包数)≥l0、生物燃料或职业暴露史。排除标准：1)3月内急性肺部疾病病史；2)其他慢性肺部疾病病史(如支气管扩张、肺间质纤维化)；3)恶性肿瘤病史；4)妊娠及哺乳期患妇女。患者入组后进行静脉采血，采集约5mL血液至抗凝采血管中并尽快离心(4℃、3000rpm、10min)，将上层血浆存放于-80℃冰箱。为了检测较低浓度的血浆蛋白，按照制造商的说明，使用去除人类14种高丰度蛋白质和结构蛋白质。胰蛋白酶消化蛋白质后，用高PH反相高效液相色谱法分离肽段。使用Q-Exactive质谱仪(Thermo)和Easy-nanoLC 1200系统进行数据依赖采集和数据独立采集分析。血浆样品的光谱库由Human UniProt蛋白数据库中的原始MS文件构建，并使用Proteome Discoverer(V2.1.0.81)进行分析。通过蛋白质相对定量分析，将光谱库和DIA的原始数据加载到Spectranaut Pulsar X软件中。使用t-检验后p值＜0.05并且表达水平倍数变化>1.2或<0.83作为处理DIA数据的标准筛选出频繁急性加重组和非频繁急性加重组之间的差异蛋白质。
结果得到：两组患者的血浆蛋白质经过质谱分析共筛选出47个差异表达蛋白质。其中20个蛋白质呈表达上调，27个蛋白质呈表达下调(图2)。
实施例2
对实施例1筛选出47个差异表达蛋白质进行GO富集分析、KEGG信号通路富集分析和ROC曲线分析。
具体过程如下：使用Metascape(http://metascape.org)进行GO富集分析和KEGG信号通路分析。使用SPSS软件进行ROC曲线分析。
GO富集分析结果如图3所示，其中生物学过程主要富集在以下方面:中性粒细胞脱粒、细胞或亚细胞组分的运动和免疫反应。此外，细胞成分的变化与胞外囊泡、细胞外空间和细胞外区域有关。此外，分子功能的变化与蛋白质同型二聚化活性、核糖核酸酶活性和核酸内切酶活性有关。
KEGG信号通路富集分析结果如图4所示，其中差异蛋白主要参与补体和凝血级联反应、细菌侵袭上皮细胞以及精氨酸和脯氨酸代谢。
ROC曲线分析结果如图5所示，11个差异蛋白质的AUC>0.7，包括：间α-胰蛋白酶抑制因子重链H3、淋巴管内皮透明质酸受体1、对氧磷酶1、丙氨酸乙醛酸转氨酶、免疫球蛋白κ可变区3D-11、胞裂蛋白2、载脂蛋白F、多巴胺β-羟化酶、肌肉肌酸激酶、FAM20C高尔基体相关分泌途径激酶和脂肪储存诱导跨膜蛋白1。
组合这11个差异蛋白质的ROC分析结果显示AUC为0.985(95％CI:0.966～1.000)，灵敏度为90.9％，特异性为100％(图6)，表明使用特定标志物组合能够进一步提高检测灵敏度和特异性。
实施例3
采用酶联免疫技术对部分血浆差异蛋白质进行逐个检测确定检测到的血浆差异蛋白质的浓度变化。
具体过程包括：
1)按照说明书配制好标准品溶液、检测抗体、辣根过氧化物酶标记的链霉亲和素以及洗液；
2)根据标准品数量和待测样品数量准备需要的板条数，先用300μL/孔洗液浸泡酶标板；
3)依次加入100μL血浆样品和提前配制好的各个浓度的标准品，再加入50μL检测抗体，使用封板膜封板，震荡混匀，25℃孵育90min；
5)弃去孔板内液体，每孔加入300μL洗液，等待1min后弃去洗液，用力在吸水纸上拍干，重复4次；
6)每孔加入100μL辣根过氧化物酶标记的链霉亲和素，使用新的封板膜封板，25℃震荡孵育30min；
7)弃去孔板内液体，每孔加入300μL洗液，等待1min后弃去洗液，用力在吸水纸上拍干，重复4次；
8)每孔加入100μL显色剂，25℃避光孵育20min；
9)每孔加入100μL终止液，充分混匀；
10)在酶标仪上测定OD450nm值；
11)Excel绘制标准曲线，计算血浆差异蛋白质的浓度。
慢阻肺频繁急性加重与非频繁急性加重患者的血浆差异蛋白质列表见表1。
表1慢阻肺频繁急性加重与非频繁急性加重患者血浆差异蛋白质
综上所述，本发明挖掘全新的、可用于慢阻肺稳定期检出与鉴定频繁急性加重与非频繁急性加重表型患者人群的核酸/蛋白质生物标志物，能提高检测的特异性、灵敏性和准确性，与现有的慢阻肺相关诊断与鉴别诊断检测相比，基于本发明标志物的检测所具备的诊疗特异性、监控预警性更高。
申请人声明，本发明通过上述实施例来说明本发明的详细方法，但本发明并不局限于上述详细方法，即不意味着本发明必须依赖上述详细方法才能实施。所属技术领域的技术人员应该明了，对本发明的任何改进，对本发明产品各原料的等效替换及辅助成分的添加、具体方式的选择等，均落在本发明的保护范围和公开范围之内。
Claims (10)
1.一组与慢阻肺频繁急性加重表型相关的标志物，其特征在于，所述标志物包括间α-胰蛋白酶抑制因子重链H3、淋巴管内皮透明质酸受体1、对氧磷酶1、丙氨酸乙醛酸转氨酶、免疫球蛋白κ可变区3D-11、胞裂蛋白2、载脂蛋白F、多巴胺β-羟化酶、肌肉肌酸激酶、FAM20C高尔基体相关分泌途径激酶或脂肪储存诱导跨膜蛋白1中任意一种或至少两种的组合。
2.如权利要求1所述的与慢阻肺频繁急性加重表型相关的标志物和/或检测其的物质在制备预测或辅助预测慢阻肺频繁急性加重表型的产品中的应用。
3.一组预测或辅助预测慢阻肺频繁急性加重表型的产品，其特征在于，所述产品包括检测权利要求1所述的与慢阻肺频繁急性加重表型相关的标志物的表达水平的试剂和/或设备。
4.如权利要求1所述的与慢阻肺频繁急性加重表型相关的标志物在构建慢阻肺频繁急性加重表型预测模型和/或制备慢阻肺频繁急性加重表型预测装置中的应用。
5.一种慢阻肺频繁急性加重表型预测模型，其特征在于，所述预测模型用于执行包括：
输入权利要求1所述的与慢阻肺频繁急性加重病相关的标志物的表达水平，拟合二元logistic回归模型；
利用拟合的二元logistic回归模型，计算Nomogram结果，根据模型中各个蛋白质对结局变量的贡献程度，给每个蛋白质的表达水平进行赋分，然后再将各个评分相加得到总评分，最后通过总评分与结局事件发生概率之间的函数转换关系，计算出受试者是慢阻肺频繁急性加重表型的预测值。
6.一种慢阻肺频繁急性加重表型预测装置，其特征在于，所述装置包括检测单元和评估单元；
所述检测单元用于执行包括：
检测受试者的待测体液样品中权利要求1所述的与慢阻肺频繁急性加重表型相关的标志物的表达水平；
所述评估单元用于执行包括：
将分析单元检测到的与慢阻肺频繁急性加重表型相关的标志物的表达水平输入权利要求5所述的慢阻肺频繁急性加重表型预测模型中进行计算，并判断是否为慢阻肺频繁急性加重患者。
7.根据权利要求6所述的慢阻肺频繁急性加重表型预测装置，其特征在于，所述待测体液样品包括外周循环血、尿液、唾液、痰液、灌洗液、汗液或体液胞外囊泡中的任意一种。
8.根据权利要求6或7所述的慢阻肺频繁急性加重表型预测装置，其特征在于，所述检测的方法包括蛋白质谱法、酶联免疫法或蛋白芯片法。
9.权利要求1所述的与慢阻肺频繁急性加重表型相关的标志物作为靶点可在筛选预防或治疗慢阻肺频繁急性加重表型药物中的应用。
10.根据权利要求9所述的应用，其特征在于，所述筛选包括基于候选药物使用前和使用后对所述与慢阻肺频繁急性加重表型相关标志物的影响，从而确定候选药物是否可以用于预防或治疗慢阻肺频繁急性加重表型。
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202310784687.1A CN117110617A (zh) | 2023-06-29 | 2023-06-29 | 一组与慢阻肺频繁急性加重表型相关的标志物及其应用 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202310784687.1A CN117110617A (zh) | 2023-06-29 | 2023-06-29 | 一组与慢阻肺频繁急性加重表型相关的标志物及其应用 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN117110617A true CN117110617A (zh) | 2023-11-24 |
Family
ID=88804519
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202310784687.1A Pending CN117110617A (zh) | 2023-06-29 | 2023-06-29 | 一组与慢阻肺频繁急性加重表型相关的标志物及其应用 |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN117110617A (zh) |
-
2023
- 2023-06-29 CN CN202310784687.1A patent/CN117110617A/zh active Pending
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US8697370B2 (en) | Biomarker for diagnosis, prediction and/or prognosis of sepsis and uses thereof | |
| US20180106817A1 (en) | Protein biomarkers and therapeutic targets for renal disorders | |
| Bennett et al. | NGAL distinguishes steroid sensitivity in idiopathic nephrotic syndrome | |
| JP2019200210A (ja) | 自閉症スペクトラム障害のリスクを決定するための方法およびシステム | |
| Dawson et al. | Urinary proteomics to support diagnosis of stroke | |
| WO2011032109A1 (en) | Biomarkers for spinal muscular atrophy | |
| US10859573B2 (en) | Nourin molecular biomarkers diagnose angina patients with negative troponin | |
| US20130210667A1 (en) | Biomarkers for Predicting Kidney and Glomerular Pathologies | |
| WO2012068545A1 (en) | Ngal in acute kidney injury | |
| WO2011044142A1 (en) | Peripheral blood biomarkers for idiopathic interstitial pneumonia and methods of use | |
| Riccio et al. | Plasma Galectin-3 and urine proteomics predict FEV1 improvement in omalizumab-treated patients with severe allergic asthma: Results from the PROXIMA sub-study | |
| CN111279193A (zh) | 利用尿代谢组分析诊断白塞氏病的方法 | |
| Deng et al. | Multi-omics approach identifies PI3 as a biomarker for disease severity and hyper-keratinization in psoriasis | |
| Liang et al. | Novel liquid chromatography-mass spectrometry for metabolite biomarkers of acute lung injury disease | |
| WO2014138583A1 (en) | Compositions and methods related to obstructive sleep apnea | |
| WO2021116057A1 (en) | Biomarker panel for diagnosing colorectal cancer | |
| Chen et al. | Plasma protein profiling by proximity extension assay technology reveals novel biomarkers of traumatic brain injury—a pilot study | |
| CN117110617A (zh) | 一组与慢阻肺频繁急性加重表型相关的标志物及其应用 | |
| CN111808941B (zh) | 一种与肺纤维化辅助诊断相关的外周血circRNA标志物及其应用 | |
| Tan et al. | Growth differentiation factor 15 is an early predictor for persistent organ failure and mortality in acute pancreatitis | |
| US20180275135A1 (en) | Biomarker panel to identify steroid resistance in childhood idiopathic nephrotic syndrome | |
| KR102519776B1 (ko) | 류마티스 관절염의 진단 및 발병 예측용 바이오마커 | |
| CN113552369B (zh) | 蛋白标志物联合用于2型糖尿病、2型糖尿病肾病的诊断的用途 | |
| US20240241139A1 (en) | Diagnosis of autism spectrum disorder by multiomics platform | |
| Liu et al. | Identification of urinary peptides associated with allergic rhinitis |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination |