Proteomic Profiles and Biological Processes of Relapsed vs. Non-Relapsed Pediatric Hodgkin Lymphoma
Abstract
:1. Introduction
2. Results
2.1. Plasma Protein Profiling
2.2. Functional Annotation of Differentially Abundant Proteins
2.3. Analysis of Biological Processes
3. Discussion
4. Materials and Methods
4.1. Research Ethics Statement
4.2. Patients and Plasma Samples
4.3. Protein Extraction and Digestion
4.4. LC-MS/MS and Label-Free Proteomic Profiling
4.5. Immunoblotting
4.6. Protein Functional Annotation
4.7. Biological Process Classification
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
2DE | two-dimensional electrophoresis |
DIGE | difference gel electrophoresis |
ECM | extracellular matrix |
HL | Hodgkin lymphoma |
LC-MS/MS | liquid chromatography mass spectrometry |
References
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Group | Disease Status | Patient no. | Sex a | Age at Diagnosis, Years | Stage b | Systemic Symptoms | LH2004 Therapeutic Group |
---|---|---|---|---|---|---|---|
Explorative | NR | 1 | M | 16 | 4 | Yes | 3 |
2 | F | 14 | 4 | No | 3 | ||
3 | F | 15 | 2 | No | 1 | ||
R | 1 | M | 13 | 2 | Yes | 3 | |
2 | F | 15 | 2 | No | 3 | ||
3 | M | 12 | 2 | No | 3 | ||
Validation | NR | 1 | M | 16 | 4 | Yes | 3 |
2 | F | 13 | 2 | No | 2 | ||
3 | F | 15 | 2 | No | 1 | ||
R | 1 | M | 13 | 2 | Yes | 3 | |
2 | F | 15 | 2 | No | 3 | ||
3 | M | 12 | 2 | No | 3 |
UniProtKB ID | Gene | Protein | Subcellular Localization | FC |
---|---|---|---|---|
More abundant in non-relapsing HL | ||||
A0A0J9YXX1 | IGHV5-10-1 | Immunoglobulin heavy variable 5-10-1 | secreted, cell membrane | 0.80 |
P01861 | IGHG4 | Immunoglobulin heavy constant γ 4 | secreted, cell membrane | 0.78 |
P08603 | CFH | Complement factor H | secreted | 0.79 |
P02765 | AHSG | α-2-HS-glycoprotein | secreted | 0.79 |
P01871 | IGHM | Immunoglobulin heavy constant mu | secreted, cell membrane | 0.78 |
P01619 | IGKV3-20 | Immunoglobulin kappa variable 3-20 | secreted, cell membrane | 0.78 |
P02649 | APOE | Apolipoprotein E | secreted | 0.78 |
P02654 | APOC1 | Apolipoprotein C-I | secreted | 0.77 |
P01031 | C5 | Complement C5 | secreted | 0.77 |
P27918 | CFP | Properdin | secreted | 0.76 |
P02766 | TTR | Transthyretin° | secreted, lysosome | 0.75 |
P00751 | CFB | Complement factor B | secreted | 0.73 |
P04196 | HRG | Histidine-rich glycoprotein° | secreted | 0.71 |
P02790 | HPX | Hemopexin | secreted | 0.68 |
P49959 | MRE11 | Double-strand break repair protein MRE11 | nucleus | 0.68 |
P19827 | ITIH1 | Inter-α-trypsin inhibitor heavy chain H1 | secreted | 0.68 |
P08697 | SERPINF2 | α-2-antiplasmin° | secreted | 0.67 |
P00747 | PLG | Plasminogen | secreted | 0.67 |
Q03591 | CFHR1 | Complement factor H-related protein 1 | secreted | 0.66 |
P0C0L5 | C4B | Complement C4-B | secreted | 0.64 |
O75636 | FCN3 | Ficolin-3 | secreted | 0.63 |
P15169 | CPN1 | Carboxypeptidase N catalytic chain | extracellular space | 0.61 |
P04004 | VTN | Vitronectin* | extracellular space | 0.61 |
P06396 | GSN | Gelsolin | cytoskeleton, secreted | 0.56 |
Q12805 | EFEMP1 | EGF-containing fibulin-like extracellular matrix protein 1° | extracellular space, extracellular matrix (ECM) | 0.58 |
P0C0L4 | C4A | Complement C4-A | secreted | 0.59 |
O14791 | APOL1 | Apolipoprotein L1 | secreted | 0.58 |
P00734 | F2 | Prothrombin | extracellular space | 0.58 |
P07358 | C8B | Complement component C8 β chain | secreted | 0.57 |
P10909 | CLU | Clusterin | nucleus, microsome, endoplasmic reticulum, cytosol, mitochondrion, nucleus | 0.56 |
Q08380 | LGALS3BP | Galectin-3-binding protein | secreted, ECM | 0.55 |
P23142 | FBLN1 | Fibulin-1° | ECM | 0.54 |
Q06033 | ITIH3 | Inter-α-trypsin inhibitor heavy chain H3 | secreted | 0.52 |
P00736 | C1R | Complement C1r subcomponent | secreted | 0.51 |
Q15485 | FCN2 | Ficolin-2 | secreted, ECM | 0.50 |
P05546 | SERPIND1 | Heparin cofactor 2 | endoplasmic reticulum, extracellular exosome | 0.50 |
P02746 | C1QB | Complement C1q subcomponent subunit B° | secreted | 0.50 |
P02747 | C1QC | Complement C1q subcomponent subunit C | secreted | 0.48 |
P01591 | JCHAIN | Immunoglobulin J chain | secreted | 0.47 |
P02760 | AMBP | Protein AMBP | secreted | 0.46 |
Q9BXR6 | CFHR5 | Complement factor H-related protein 5 | secreted | 0.45 |
P07225 | PROS1 | Vitamin K-dependent protein S | secreted | 0.44 |
P02652 | APOA2 | Apolipoprotein A-II | secreted | 0.42 |
P01008 | SERPINC1 | Antithrombin III*° | extracellular space | 0.39 |
P00748 | F12 | Coagulation factor XII | secreted | 0.36 |
P20742 | PZP | Pregnancy zone protein° | secreted | 0.36 |
P02745 | C1QA | Complement C1q subcomponent subunit A | secreted | 0.31 |
P01019 | AGT | Angiotensinogen° | secreted | 0.28 |
A0A0C4DH68 | IGKV2-24 | Immunoglobulin kappa variable 2-24 | secreted, cell membrane | 0.26 |
P04180 | LCAT | Phosphatidylcholine-sterol acyltransferase | secreted | 0.26 |
P24593 | IGFBP5 | Insulin-like growth factor-binding protein 5 | secreted | 0.26 |
P22792 | CPN2 | Carboxypeptidase N subunit 2 | secreted | 0.26 |
P68871 | HBB | Hemoglobin subunit β | cytosol, extracellular region, secreted | 0.26 |
P0DP03 | IGHV3-30-5 | Immunoglobulin heavy variable 3-30-5 | secreted, cell membrane | 0.26 |
P08709 | F7 | Coagulation factor VII | secreted | 0.23 |
P01009 | SERPINA1 | α-1-antitrypsin*° | secreted, endoplasmic reticulum | 0.23 |
P19823 | ITIH2 | Inter-α-trypsin inhibitor heavy chain H2 | secreted | 0.10 |
Q92496 | CFHR4 | Complement factor H-related protein 4 | secreted | 0.09 |
P48740 | MASP1 | Mannan-binding lectin serine protease 1 | secreted | 0.08 |
P27169 | PON1 | Serum paraoxonase/arylesterase 1° | extracellular space | 0.08 |
More abundant in relapsing HL | ||||
P02751 | FN1 | Fibronectin° | ECM | 19.61 |
P06702 | S100A9 | Protein S100-A9 | cytoskeleton, extracellular region, cytoskeleton, secreted, cell membrane | 15.33 |
P35908 | KRT2 | Keratin, type II cytoskeletal 2 epidermal | cytoskeleton, cytosol, endoplasmic reticulum, nucleus, cell membrane | 9.45 |
P0DJI8 | SAA1 | Serum amyloid A-1 protein | secreted | 5.37 |
Q15848 | ADIPO | Adiponectin | secreted | 4.73 |
P36955 | SERPINF1 | Pigment epithelium-derived factor | secreted | 3.51 |
Q9H5I5 | PIEZO2 | Piezo-type mechanosensitive ion channel component 2 | membrane | 3.10 |
Q9Y490 | TLN1 | Talin-1° | cytoskeleton, cell membrane, cell surface | 3.10 |
P0DJI9 | SAA2 | Serum amyloid A-2 protein | secreted | 3.06 |
P09871 | C1S | Complement C1s subcomponent° | extracellular space | 3.05 |
P04264 | KRT1 | Keratin, type II cytoskeletal 1 | cell membrane | 3.02 |
P02753 | RBP4 | Retinol-binding protein 4 | secreted | 2.77 |
Q86YZ3 | HRNR | Hornerin | cytoplasmic granules | 2.62 |
P02671 | FGA | Fibrinogen α chain* | secreted | 2.27 |
P02741 | CRP | C-reactive protein | secreted | 2.19 |
P02656 | APOC3 | Apolipoprotein C-III | secreted | 2.12 |
P02675 | FGB | Fibrinogen β chain*° | secreted | 2.06 |
P01700 | IGLV1-47 | Immunoglobulin lambda variable 1-47 | secreted, membrane | 2.03 |
P05160 | F13B | Coagulation factor XIII B chain | secreted | 2.03 |
P35527 | KRT9 | Keratin, type I cytoskeletal 9 | cytosol, extracellular exosome, nucleus, membrane | 2.02 |
P00450 | CP | Ceruloplasmin* | secreted | 2.01 |
P05156 | CFI | Complement factor I | secreted | 1.95 |
P10643 | C7 | Complement component C7 | secreted | 1.95 |
P02679 | FGG | Fibrinogen γ chain*° | secreted | 1.94 |
P07360 | C8G | Complement component C8 γ chain | secreted | 1.86 |
P02748 | C9 | Complement component C9 | secreted | 1.80 |
P07996 | THBS1 | Thrombospondin-1° | endoplasmic reticulum secreted, ECM, cell surface | 1.73 |
P63261 | ACTG1 | Actin, cytoplasmic 2 | cytoskeleton | 1.57 |
IGLC2_HUMAN | IGLC2 | Immunoglobulin lambda constant 2 | secreted, cell membrane | 1.37 |
P18428 | LBP | Lipopolysaccharide-binding protein | secreted, cytoplasmic granule membrane | 1.36 |
P04217 | A1BG | α-1B-glycoprotein° | secreted | 1.35 |
LV39_HUMAN | IGLV3-9 | Immunoglobulin lambda variable 3-9 | secreted, cell membrane | 1.34 |
UniProtKB ID | Protein Name (Gene Symbol) (a) | Biological Processes (DAVID) (p < 0.01) (b) | Biological Classes | Regulatory Subclasses |
---|---|---|---|---|
More abundant in non-relapsing HL (n = 11) | ||||
P01019 | Angiotensinogen (AGT) | negative regulation of endopeptidase activity, regulation of blood vessel size by renin-angiotensin | transport and homeostasis, regulation, vascularization, response, cell and ECM organization, lipid metabolism, protein metabolism | immune system, transport and homeostasis, vascularization, response, cell and ECM organization, cell death, lipid metabolism, protein metabolism, signaling |
P02746 | Complement C1q subcomponent subunit B (C1QB) | complement activation, proteolysis, complement activation (classical pathway), innate immune response | immune system, regulation, transport and homeostasis, response, protein metabolism | immune system, response, protein metabolism |
Q12805 | EGF-containing fibulin-like extracellular matrix protein 1 (EFEMP1) | NA | regulation, transport and homeostasis, response, protein metabolism | response, signaling |
P23142 | Fibulin-1 (FBLN1) | negative regulation of cell adhesion | regulation, transport and homeostasis, coagulation, response, cell and ECM organization, protein metabolism | immune system, transport and homeostasis, response, cell and ECM organization, protein metabolism, signaling |
P04196 | Histidine-rich glycoprotein (HRG) | negative regulation of endopeptidase activity, platelet degranulation, negative regulation of fibrinolysis, negative regulation of cell adhesion, fibrinolysis | immune system, regulation, transport and homeostasis, coagulation, fibrinolysis, response, cell and ECM organization | immune system, transport and homeostasis, coagulation, fibrinolysis, response, cell and ECM organization, cell death, protein metabolism, signaling |
P27169 | Serum paraoxonase/ arylesterase 1 (PON1) | negative regulation of plasma lipoprotein particle oxidation, cholesterol metabolic process, phosphatidylcholine metabolic process, | regulation, response, lipid metabolism | transport and homeostasis |
P20742 | Pregnancy zone protein (PZP) | negative regulation of endopeptidase activity | regulation | protein metabolism |
P01009 | α-1-antitrypsin* (SERPINA1) | acute-phase response, ER to Golgi vesicle-mediated transport, platelet degranulation, blood coagulation, negative regulation of endopeptidase activity | immune system, regulation, transport and homeostasis, coagulation, response, protein metabolism | transport and homeostasis, protein metabolism |
P01008 | Antithrombin III* (SERPINC1) | negative regulation of endopeptidase activity, blood coagulation | immune system, regulation, transport and homeostasis, coagulation, response, protein metabolism | coagulation, response, protein metabolism |
P08697 | α-2-antiplasmin (SERPINF2) | acute-phase response, negative regulation of endopeptidase activity, platelet degranulation, fibrinolysis, regulation of blood vessel size by renin-angiotensin | immune system, regulation, transport and homeostasis, coagulation, fibrinolysis, response, cell and ECM organization, protein metabolism | immune system, transport and homeostasis, coagulation, fibrinolysis, vascularization, response, cell and ECM organization, protein metabolism, signaling |
P02766 | Transthyretin (TTR) | retinoid metabolic process, cellular protein metabolic process, | immune system, regulation, transport and homeostasis, response, cell and ECM organization, protein metabolism | transport and homeostasis, response, signaling |
More abundant in relapsing HL (n = 7) | ||||
P04217 | α-1B-glycoprotein (A1BG) | platelet degranulation | immune system, transport and homeostasis, coagulation, response | none |
P09871 | Complement C1s subcomponent (C1S) | proteolysis, complement activation, complement activation (classical pathway), innate immune response | immune system, regulation, response, protein metabolism | immune system, response, protein metabolism |
P02675 | Fibrinogen β chain* (FGB) | platelet degranulation, innate immune response, response to calcium ion, fibrinolysis, blood coagulation, fibrin clot formation, platelet aggregation, positive regulation of peptide hormone secretion, plasminogen activation, positive regulation of heterotypic cell-cell adhesion, protein polymerization, cellular protein complex assembly, ECM organization, positive regulation of exocytosis, negative regulation of endothelial cell apoptotic process, platelet activation, positive regulation of vasoconstriction, positive regulation of substrate adhesion-dependent cell spreading, negative regulation of extrinsic apoptotic signaling pathway via death domain receptors, induction of bacterial agglutination | immune system, regulation, transport and homeostasis, coagulation, fibrinolysis, response, cell and ECM organization, protein metabolism | immune system, transport and homeostasis, coagulation, vascularization, response, cell and ECM organization, cell death, protein metabolism, signaling |
P02679 | Fibrinogen γ chain* (FGG) | platelet degranulation, innate immune response, response to calcium ion, fibrinolysis, blood coagulation, fibrin clot formation, platelet aggregation, positive regulation of peptide hormone secretion, plasminogen activation, positive regulation of heterotypic cell-cell adhesion, protein polymerization, cellular protein complex assembly, ECM organization, positive regulation of exocytosis, negative regulation of endothelial cell apoptotic process, platelet activation, positive regulation of vasoconstriction, positive regulation of substrate adhesion-dependent cell spreading, negative regulation of extrinsic apoptotic signaling pathway via death domain receptors, induction of bacterial agglutination | immune system, regulation, transport and homeostasis, coagulation, fibrinolysis, response, cell and ECM organization, protein metabolism | immune system, transport and homeostasis, coagulation, vascularization, response, cell and ECM organization, cell death, signaling, protein metabolism |
P02751 | Fibronectin (FN1) | platelet degranulation, acute-phase response, ECM organization | immune system, regulation, transport and homeostasis, coagulation, response, cell and ECM organization | immune system, transport and homeostasis, response, cell and ECM organization, cell death, lipid metabolism, signaling |
P07996 | Thrombospondin-1 (THBS1) | ECM organization, response to calcium ion, immune response, platelet degranulation, response to calcium ion, inflammatory response | immune system, regulation, transport and homeostasis, coagulation, response, cell and ECM organization, protein metabolism | immune system, transport and homeostasis, coagulation, vascularization, response, cell and ECM organization, cell death, protein metabolism, signaling |
Q9Y490 | Talin-1 (TLN1) | platelet degranulation, platelet aggregation | regulation, transport and homeostasis, coagulation, response, cell and ECM organization, protein metabolism | cell and ECM organization |
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Repetto, O.; De Re, V.; Mussolin, L.; Tedeschi, M.; Elia, C.; Bianchi, M.; Buffardi, S.; Sala, A.; Burnelli, R.; Mascarin, M. Proteomic Profiles and Biological Processes of Relapsed vs. Non-Relapsed Pediatric Hodgkin Lymphoma. Int. J. Mol. Sci. 2020, 21, 2185. https://doi.org/10.3390/ijms21062185
Repetto O, De Re V, Mussolin L, Tedeschi M, Elia C, Bianchi M, Buffardi S, Sala A, Burnelli R, Mascarin M. Proteomic Profiles and Biological Processes of Relapsed vs. Non-Relapsed Pediatric Hodgkin Lymphoma. International Journal of Molecular Sciences. 2020; 21(6):2185. https://doi.org/10.3390/ijms21062185
Chicago/Turabian StyleRepetto, Ombretta, Valli De Re, Lara Mussolin, Massimo Tedeschi, Caterina Elia, Maurizio Bianchi, Salvatore Buffardi, Alessandra Sala, Roberta Burnelli, and Maurizio Mascarin. 2020. "Proteomic Profiles and Biological Processes of Relapsed vs. Non-Relapsed Pediatric Hodgkin Lymphoma" International Journal of Molecular Sciences 21, no. 6: 2185. https://doi.org/10.3390/ijms21062185