Defining the Inflammatory Plasma Proteome in Pediatric Hodgkin Lymphoma

被引:7
作者
Agrusa, Jennifer E. [1 ]
Scull, Brooks P. [1 ]
Abhyankar, Harshal A. [1 ]
Lin, Howard [1 ]
Ozuah, Nmazuo W. [1 ]
Chakraborty, Rikhia [1 ]
Eckstein, Olive S. [1 ]
Gulati, Nitya [1 ]
Fattah, Elmoataz Abdel [1 ]
El-Mallawany, Nader K. [1 ]
Rouce, Rayne H. [1 ]
Dreyer, ZoAnn E. [1 ]
Brackett, Julienne [1 ]
Margolin, Judith F. [1 ]
Lubega, Joseph [1 ]
Horton, Terzah M. [1 ]
Bollard, Catherine M. [2 ,3 ]
Gramatges, M. Monica [1 ]
Kamdar, Kala Y. [1 ]
McClain, Kenneth L. [1 ]
Man, Tsz-Kwong [1 ]
Allen, Carl E. [1 ]
机构
[1] Baylor Coll Med, Texas Childrens Canc & Hematol Ctr, Dept Pediat, Houston, TX 77030 USA
[2] Childrens Natl Hlth Syst, Ctr Canc & Immunol Res, Washington, DC 20010 USA
[3] George Washington Univ, Washington, DC 20010 USA
关键词
Hodgkin lymphoma; childhood hematological malignancies; immunology; chemokines; cytokines; INTERCELLULAR-ADHESION MOLECULE-1; INTERNATIONAL PROGNOSTIC SCORE; SERUM-LEVELS; TREATMENT RESPONSE; INTERFERON-GAMMA; PREDICT RESPONSE; RISK; EXPRESSION; CHILDREN; DISEASE;
D O I
10.3390/cancers12123603
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Simple Summary Hodgkin lymphoma (HL) is a common type of cancer that is characterized by rare, malignant cells among an inflammatory microenvironment. Specific systemic, inflammatory plasma proteins have demonstrated prognostic significance in adult HL; however, systemic inflammation has not been well-characterized in childhood HL. The aim of our study was to better define the inflammatory pre-therapy plasma proteome and identify plasma proteins associated with clinical features of childhood HL. We measured plasma concentrations of 135 proteins in 56 pediatric subjects with newly diagnosed HL and 47 healthy pediatric controls. We found that the plasma protein profile was distinct from controls, and unique proteins were associated with high-risk disease (IL-10, TNF-alpha, IFN-gamma, IL-8), slow early therapy response (CCL13, IFN-lambda 1, IL-8), and relapse (TNFSF10). These proteins could be used to improve risk stratification, and thus optimize outcomes and minimize unnecessary toxic exposures for those with childhood HL. Hodgkin lymphoma (HL) histopathology is characterized by rare malignant Reed-Sternberg cells among an inflammatory infiltrate. We hypothesized that characteristics of inflammation in pediatric HL lesions would be reflected by the levels of inflammatory cytokines or chemokines in pre-therapy plasma of children with HL. The study objectives were to better define the inflammatory pre-therapy plasma proteome and identify plasma biomarkers associated with extent of disease and clinical outcomes in pediatric HL. Pre-therapy plasma samples were obtained from pediatric subjects with newly diagnosed HL and healthy pediatric controls. Plasma concentrations of 135 cytokines/chemokines were measured with the Luminex platform. Associations between protein concentration and disease characteristics were determined using multivariate permutation tests with false discovery control. Fifty-six subjects with HL (mean age: 13 years, range 3-18) and 47 controls were analyzed. The cytokine/chemokine profiles of subjects with HL were distinct from controls, and unique cytokines/chemokines were associated with high-risk disease (IL-10, TNF-alpha, IFN-gamma, IL-8) and slow early response (CCL13, IFN-lambda 1, IL-8). TNFSF10 was significantly elevated among those who ultimately relapsed and was significantly associated with worse event-free survival. These biomarkers could be incorporated into biologically based risk stratification to optimize outcomes and minimize toxicities in pediatric HL.
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收藏
页码:1 / 13
页数:13
相关论文
共 51 条
[1]   Serum level of intercellular adhesion molecule-1 in children with malignant lymphoma [J].
Abdelrazik, Nabil ;
Fouda, Manal ;
Zaghloul, Mohammad Hosam El-deen ;
Abbas, Dalia .
MEDICAL PRINCIPLES AND PRACTICE, 2008, 17 (03) :233-238
[2]   CD68 staining correlates with the size of residual mass but not with survival in classical Hodgkin lymphoma [J].
Agur, Ariel ;
Amir, Gail ;
Paltiel, Ora ;
Klein, Martine ;
Dann, Eldad J. ;
Goldschmidt, Hanoch ;
Goldschmidt, Neta .
LEUKEMIA & LYMPHOMA, 2015, 56 (05) :1315-1319
[3]   Minimal Treatment of Low-Risk, Pediatric Lymphocyte-Predominant Hodgkin Lymphoma: A Report From the Children's Oncology Group [J].
Appel, Burton E. ;
Chen, Lu ;
Buxton, Allen B. ;
Hutchison, Robert E. ;
Hodgson, David C. ;
Ehrlich, Peter F. ;
Constine, Louis S. ;
Schwartz, Cindy L. .
JOURNAL OF CLINICAL ONCOLOGY, 2016, 34 (20) :2372-U114
[4]   Biological markers may add to prediction of outcome achieved by the international prognostic score in Hodgkin's disease [J].
Axdorph, U ;
Sjöberg, J ;
Grimfors, G ;
Landgren, O ;
Porwit-MacDonald, A ;
Björkholm, M .
ANNALS OF ONCOLOGY, 2000, 11 (11) :1405-1411
[5]   NEUTROPHIL-ACTIVATING PEPTIDE-1 INTERLEUKIN-8, A NOVEL CYTOKINE THAT ACTIVATES NEUTROPHILS [J].
BAGGIOLINI, M ;
WALZ, A ;
KUNKEL, SL .
JOURNAL OF CLINICAL INVESTIGATION, 1989, 84 (04) :1045-1049
[6]   TNF-α in promotion and progression of cancer [J].
Balkwill, Frances .
CANCER AND METASTASIS REVIEWS, 2006, 25 (03) :409-416
[7]   Serum VEGF as a significant marker of treatment response in Hodgkin lymphoma [J].
Ben Arush, M. Weyl ;
Ben Barak, A. ;
Maurice, S. ;
Livne, E. .
PEDIATRIC HEMATOLOGY AND ONCOLOGY, 2007, 24 (02) :111-115
[8]   Pre-treatment serum levels of interleukin-10, interleukin-12 and their ratio predict response to therapy and probability of event-free and overall survival in childhood soft tissue sarcomas, Hodgkin's lymphomas and acute lymphoblastic leukemias [J].
Bien, Ewa ;
Balcerska, Anna ;
Adamkiewicz-Drozynska, Elzbieta ;
Rapala, Malgorzata ;
Krawczyk, Malgorzata ;
Stepinski, Jan .
CLINICAL BIOCHEMISTRY, 2009, 42 (10-11) :1144-1157
[9]  
Blanpain C, 1999, BLOOD, V94, P1899
[10]   Plasma cytokine and soluble receptor signature predicts outcome of patients with classical Hodgkin's lymphoma:: A study from the Groupe d'Etude des Lymphomes de l'Adulte [J].
Casasnovas, Rene-Olivier ;
Mounier, Nicolas ;
Brice, Pauline ;
Divine, Marine ;
Morschhauser, Franck ;
Gabarre, Jean ;
Blay, Jean-Yves ;
Voillat, Laurent ;
Lederlin, Pierre ;
Stamatoullas, Aspasia ;
Bienvenu, Jacques ;
Guiguet, Michel ;
Intrator, Liliane ;
Grandjean, Monique ;
Briere, Josette ;
Ferme, Christophe ;
Salles, Gilles .
JOURNAL OF CLINICAL ONCOLOGY, 2007, 25 (13) :1732-1740