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Defining the Inflammatory Plasma Proteome in Pediatric Hodgkin Lymphoma

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Defining the Inflammatory Plasma Proteome in Pediatric Hodgkin Lymphoma Cancers 2020, 12, 3603 S1 of S15 Supplementary Materials: Defining the Inflammatory Plasma Proteome in Pediatric Hodgkin Lymphoma Jennifer E. Agrusa, Brooks P. Scull, Harshal A. Abhyankar, Howard Lin, Nmazuo W. Ozuah, Rikhia Chakraborty, Olive S. Eckstein, Nitya Gulati, Elmoataz Abdel Fattah, Nader K. El- Mallawany, Rayne H. Rouce, ZoAnn E. Dreyer, Julienne Brackett, Judith F. Margolin, Joseph Lubega, Terzah M. Horton, Catherine M. Bollard, M. Monica Gramatges, Kala Y. Kamdar, Kenneth L. McClain, Tsz-Kwong Man and Carl E. Allen Figure S1. Event-free survival for subjects enrolled on TXCH-HD-12A (n = 40). Four subjects (10%) within this cohort relapsed, all within two years of diagnosis. Cancers 2020, 12, 3603 S2 of S15 Figure S2. Significant cytokines/chemokines identified when comparing between subgroups were not statistically different comparing all HL vs. controls due to “dilution” of analyte levels from smaller HL subgroups. Table S1. Demographic and Clinical Features of Individual HL Subjects. F, female; M, male; NOS, not otherwise specified; LP, nodular lymphocyte predominant; LR, lymphocyte-rich; MC, mixed cellularity; NS, nodular sclerosing; LR/IR, low-risk/intermediate-risk; HR, high-risk; RER, rapid early responder; SER, slow early responder. Subject Gender Age Clinical Diagnosis Ethnicity Risk Response to Therapy Relapse HL01 F 14 CLASSICAL NOS Hispanic HR RER No HL02 M 12 CLASSICAL NOS non-Hispanic black LR/IR RER No HL03 M 11 CLASSICAL NOS non-Hispanic white LR/IR RER No HL04 M 12 CLASSICAL NOS Hispanic LR/IR SER No Cancers 2020, 12, 3603 S3 of S15 HL05 F 17 CLASSICAL NOS non-Hispanic white LR/IR SER No HL06 F 8 LP Hispanic LR/IR RER No HL07 F 13 LP non-Hispanic white LR/IR RER No HL08 M 11 LP non-Hispanic black LR/IR RER Yes HL09 M 3 LR Hispanic LR/IR RER No HL10 M 9 MC Hispanic HR SER No HL11 M 13 MC Hispanic HR RER No HL12 F 11 MC non-Hispanic white HR RER No HL13 M 13 MC non-Hispanic black HR RER Yes HL14 M 7 MC non-Hispanic black LR/IR RER No HL15 M 11 MC Hispanic LR/IR RER No HL16 F 10 MC Hispanic LR/IR RER No HL17 M 9 MC non-Hispanic white LR/IR RER No HL18 M 17 MC non-Hispanic white LR/IR RER No HL19 M 11 MC non-Hispanic white LR/IR RER No HL20 F 11 MC non-Hispanic white LR/IR RER No HL21 F 15 MC non-Hispanic white LR/IR RER Yes HL22 M 14 NS Hispanic HR SER No HL23 M 17 NS Hispanic HR RER No HL24 F 13 NS Hispanic HR SER No HL25 F 17 NS non-Hispanic white HR RER No HL26 M 12 NS non-Hispanic white HR RER No HL27 M 12 NS Hispanic HR SER No HL28 M 15 NS non-Hispanic Asian HR SER Yes HL29 M 17 NS non-Hispanic black HR SER Yes HL30 M 5 NS Hispanic LR/IR RER No HL31 F 6 NS Hispanic LR/IR RER No HL32 F 13 NS Hispanic LR/IR RER No HL33 M 9 NS non-Hispanic white LR/IR RER No HL34 M 17 NS Hispanic LR/IR RER No HL35 F 12 NS Hispanic LR/IR RER No HL36 M 18 NS Hispanic LR/IR RER No HL37 F 15 NS Hispanic LR/IR RER No HL38 M 12 NS non-Hispanic white LR/IR RER No HL39 F 7 NS Hispanic LR/IR RER No HL40 M 16 NS non-Hispanic white LR/IR RER No HL41 M 16 NS Hispanic LR/IR RER No HL42 F 17 NS non-Hispanic white LR/IR RER No HL43 F 17 NS non-Hispanic black LR/IR RER No HL44 M 7 NS Hispanic LR/IR SER No HL45 M 11 NS non-Hispanic white LR/IR RER No HL46 M 16 NS non-Hispanic white LR/IR SER No HL47 F 16 NS Hispanic LR/IR RER No HL48 M 16 NS non-Hispanic white LR/IR RER No HL49 F 16 NS Hispanic LR/IR RER No HL50 M 13 NS non-Hispanic black LR/IR RER No HL51 F 16 NS non-Hispanic white LR/IR RER No HL52 F 13 NS non-Hispanic black LR/IR RER No HL53 F 14 NS non-Hispanic white LR/IR RER Yes HL54 M 17 NS non-Hispanic Asian LR/IR RER Yes HL55 F 17 NS non-Hispanic white LR/IR RER Yes HL56 F 18 NS non-Hispanic black LR/IR RER Yes Cancers 2020, 12, 3603 S4 of S15 Table S2. Demographic and Clinical Features of Individual Control Subjects. F, female; M, male; IgM, immunoglobulin Subject Gender Age Clinical Diagnosis C01 F 16 deep venous thrombosis C02 F 9 anemia C03 F 1 Von Willebrand disease C04 M 2 bruising C05 M 14 anemia C06 F 15 menorrhagia C07 F 17 menorrhagia C08 F 11 vascular malformation C09 F 12 menorrhagia C10 F 5 pyruvate kinase deficiency C11 F 12 menorrhagia C12 M 2 glucose-6-phosphate dehydrogenase (G6PD) deficiency C13 F 16 epilepsy C14 F 1 dermoid cyst, diabetes insipidus C15 F 18 acne C16 M 13 celiac disease C17 F 18 Kikuchi disease C18 F 3 dermoid cyst C19 M 8 rib fracture C20 M 12 ossifying fibroma C21 M 1 dermoid cyst C22 M 18 lymphadenopathy, not lymphoma C23 F 11 non-ossifying fibroma C24 M 13 fibrous dysplasia C25 F 9 vertebra plana (not Langerhans Cell Histiocytosis) C26 M 9 giant cell granuloma C27 F 10 unicentric Castleman disease s/p resection C28 M 6 Gorham-Stout disease C29 F 2 eczema C30 F 6 pituitary stalk tumor (not Langerhans Cell Histiocytosis) C31 F 2 dysuria C32 M 14 collapsed vertebrae C33 M 5 sibling with Langerhans Cell Histiocytosis C34 M 4 vascular malformation C35 M 2 collapsed vertebrae (not Langerhans Cell Histiocytosis) C36 F 1 dermoid cyst C37 M 10 thymic hyperplasia C38 M 17 reactive lymph node C39 M 4 eczema C40 M 5 Bartonella infection C41 M 8 allergies C42 M 15 sibling with genetic disorder C43 M 15 sibling with genetic disorder C44 M 11 desmoid-type fibromatosis C45 M 7 granulomatous lymphadenitis C46 F 19 elevated IgM C47 F 17 reactive lymph node Cancers 2020, 12, 3603 S5 of S15 Table S3. Proteins Significant in Study Cohort for (a) HL vs. Controls, (b) HR vs. LR/IR, (c) SER vs. RER, (d) Relapse vs. No Relapse. b. a. Analyte HL Control Linear p- val Analyte HR LR/IR Linear p-val Log Log Fold- Log Log Fold- Average Average Change Average Average Change Conc. ± Conc. ± (HL Conc. ± Conc. ± (HR Stdev Stdev vs. Stdev Stdev vs. (pg/mL) (pg/mL) Controls) (pg/mL) (pg/mL) LR/IR) TGF-α 6.4 ± 3.5 2.9 ± 2.2 11.11 <1E -07 IL-10 6.2 ± 2.2 3.1 ± 1.9 8.57 9.00E-06 IL-6.3 3.4 ± 2.4 0.6 ± 1.1 7.14 <1E-07 IL-8.2 5.3 ± 2.0 3.1 ± 2.1 4.52 1.93E-03 CXCL13 7.5 ± 1.8 4.9 ± 1.8 6.25 <1E-07 IFN-ɤ 4.5 ± 1.8 2.9 ± 1.5 3.01 1.89E-03 IL-6.2 3.4 ± 2.1 1.1 ± 1.4 5 <1E -07 TNF-α.2 3.8 ± 0.9 2.3 ± 1.3 2.9 3.42E-04 IL-10 3.8 ± 2.4 1.7 ± 1.2 4.35 4.00E-07 TNF-α 4.1 ± 1.2 3.0 ± 1.0 2.08 2.34E-03 CXCL9 12.0 ± 2.3 9.9 ± 1.5 4.17 8.00E-07 Analyte RER SER Linear p-val CCL19 8.8 ± 1.4 6.9 ± 0.9 4 <1E -07 c. Log Log Average Fold- CCL17 10.0 ± 1.4 8.1 ± 3.3 3.7 1.75E-04 Average Conc. ± Change FGF-23 8.2 ± 4.2 6.5 ± 2.2 3.45 1.32E-02 Conc. ± Stdev (SER Stdev (pg/mL) vs. CXCL10 10.1 ± 3.2 8.4 ± 1.4 3.13 2.45E -03 (pg/mL) RER) MIF 9.7 ± 2.4 8.1 ± 1.1 3.03 5.45E-03 CCL13 3.9 ± 1.7 6.5 ± 1.6 5.88 5.18E-05 sIL-4R 10.7 ± 1.5 9.2 ± 0.9 2.86 <1E -07 CXCL11 9.0 ± 1.6 7.6 ± 2.1 2.78 1.07E-04 IFN-λ1 5.6 ± 1.9 8.0 ± 1.3 5.26 2.84E-04 IL-9 3.6 ± 2.4 2.2 ± 1.8 2.63 1.68E-03 IL-8 1.7 ± 1.6 3.8 ± 1.3 4.17 5.45E-04 CCL2 11.9 ± 2.7 10.6 ± 2.6 2.5 1.68E -02 CCL26 7.4 ± 1.4 6.3 ± 1.6 2.27 1.33E-04 GRO-α 9.6 ± 1.5 8.4 ± 1.9 2.22 8.03E-04 Analyte No Relapse Linear p-val d. Relapse Log Fold- sIL-2Ra 12.4 ± 1.2 11.3 ± 1.9 2.17 3.69E -04 Log Average Change Leptin.2 12.7 ± 2.2 11.5 ± 2.5 2.17 1.50E-02 Average Conc. ± (Relapse Interstitial 10.5 ± 1.3 9.5 ± 1.7 2.08 6.53E-04 Conc. ± Stdev vs. Collagenase Stdev (pg/mL) No CCL21 8.3 ± 0.9 7.3 ± 1.3 1.92 5.06E-05 (pg/mL) Relapse) MUC-16 3.0 ± 1.4 2.1 ± 0.8 1.82 3.62E-04 TNFSF10 6.3 ± 1.1 7.9 ± 1.4 3.03 4.84E-04 sVEGFR1 12.1 ± 1.4 11.3 ± 1.4 1.75 5.06E-03 CCL24 7.9 ± 1.4 7.1 ± 1.6 1.72 1.02E-02 Eotaxin 7.5 ± 1.3 6.7 ± 1.5 1.67 6.62E-03 Each comparison is significant at FDR=0.1.
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