| BMC Cancer | |
| The immunosignature of canine lymphoma: characterization and diagnostic application | |
| Stephen Albert Johnston1  Douglas H Thamm2  Joseph Barten Legutki1  | |
| [1] Center for Innovations in Medicine, The Biodesign Institute, Arizona State University, Tempe, AZ 85287-5901, USA | |
| [2] Flint Animal Cancer Center, Colorado State University, 300 West Drake Road, Fort Collins, CO 80523-1620, USA | |
| 关键词: Peptide microarray; Antibody response; Diagnostic; Dog; Cancer; | |
| Others : 1121097 DOI : 10.1186/1471-2407-14-657 |
|
| received in 2014-04-28, accepted in 2014-09-01, 发布年份 2014 | |
PDF
|
|
【 摘 要 】
Background
Cancer diagnosis in both dogs and humans is complicated by the lack of a non-invasive diagnostic test. To meet this clinical need, we apply the recently developed immunosignature assay to spontaneous canine lymphoma as clinical proof-of-concept. Here we evaluate the immunosignature as a diagnostic for spontaneous canine lymphoma at both at initial diagnosis and evaluating the disease free interval following treatment.
Methods
Sera from dogs with confirmed lymphoma (B cell n = 38, T cell n = 11) and clinically normal dogs (n = 39) were analyzed. Serum antibody responses were characterized by analyzing the binding pattern, or immunosignature, of serum antibodies on a non-natural sequence peptide microarray. Peptides were selected and tested for the ability to distinguish healthy dogs from those with lymphoma and to distinguish lymphoma subtypes based on immunophenotype. The immunosignature of dogs with lymphoma were evaluated for individual signatures. Changes in the immunosignatures were evaluated following treatment and eventual relapse.
Results
Despite being a clonal disease, both an individual immunosignature and a generalized lymphoma immunosignature were observed in each dog. The general lymphoma immunosignature identified in the initial set of dogs (n = 32) was able to predict disease status in an independent set of dogs (n = 42, 97% accuracy). A separate immunosignature was able to distinguish the lymphoma based on immunophenotype (n = 25, 88% accuracy). The individual immunosignature was capable of confirming remission three months following diagnosis. Immunosignature at diagnosis was able to predict which dogs with B cell lymphoma would relapse in less than 120 days (n = 33, 97% accuracy).
Conclusion
We conclude that the immunosignature can serve as a multilevel diagnostic for canine, and potentially human, lymphoma.
【 授权许可】
2014 Johnston et al.; licensee BioMed Central Ltd.
【 预 览 】
| Files | Size | Format | View |
|---|---|---|---|
| 20150211020907671.pdf | 3030KB | ||
| Figure 4. | 173KB | Image | |
| Figure 3. | 148KB | Image | |
| Figure 2. | 163KB | Image | |
| Figure 1. | 176KB | Image |
【 图 表 】
Figure 1.
Figure 2.
Figure 3.
Figure 4.
【 参考文献 】
- [1]Siegel R, Naishadham D, Jemal A: Cancer statistics, 2013. CA Cancer J Clin 2013, 63(1):11-30.
- [2]Shankland KR, Armitage JO, Hancock BW: Non-Hodgkin lymphoma. Lancet 2012, 380(9844):848-857.
- [3]Evans LS, Hancock BW: Non-Hodgkin lymphoma. Lancet 2003, 362(9378):139-146.
- [4]Larouche JF, Berger F, Chassagne-Clement C, Ffrench M, Callet-Bauchu E, Sebban C, Ghesquieres H, Broussais-Guillaumot F, Salles G, Coiffier B: Lymphoma recurrence 5 years or later following diffuse large B-cell lymphoma: clinical characteristics and outcome. J Clin Oncol 2010, 28(12):2094-2100.
- [5]Marconato L, Gelain ME, Comazzi S: The dog as a possible animal model for human non-Hodgkin lymphoma: a review. Hematol Oncol 2013, 31(1):1-9.
- [6]Ito D, Frantz AM, Modiano JF: Canine lymphoma as a comparative model for human non-Hodgkin lymphoma: recent progress and applications. Vet Immunol Immunopathol 2014, 159(3–4):192-201.
- [7]Richards KL, Motsinger-Reif AA, Chen HW, Fedoriw Y, Fan C, Nielsen DM, Small GW, Thomas R, Smith C, Dave SS, Perou CM, Breen M, Borst LB, Stuter SE: Gene profiling of canine B-cell lymphoma reveals germinal center and postgerminal center subtypes with different survival times, modeling human DLBCL. Cancer Res 2013, 73(16):5029-5039.
- [8]Paoloni M, Khanna C: Translation of new cancer treatments from pet dogs to humans. Nat Rev Cancer 2008, 8(2):147-156.
- [9]Honigberg LA, Smith AM, Sirisawad M, Verner E, Loury D, Chang B, Li S, Pan Z, Thamm DH, Miller RA, Buggy JJ: The Bruton tyrosine kinase inhibitor PCI-32765 blocks B-cell activation and is efficacious in models of autoimmune disease and B-cell malignancy. Proc Natl Acad Sci USA 2010, 107(29):13075-13080.
- [10]London CA, Bernabe LF, Barnard S, Kisseberth WC, Borgatti A, Henson M, Wilson H, Jensen K, Ito D, Modiano JF, Bear MD, Pennell ML, Saint-Martin JR, McCauley D, Kauffman M, Shacham S: Preclinical evaluation of the novel, orally bioavailable Selective Inhibitor of Nuclear Export (SINE) KPT-335 in spontaneous canine cancer: results of a phase I study. PLoS One 2014, 9(2):e87585.
- [11]Vail DM, Pinkerton ME, Young KM: Canine lymphoma and lymphoid leukemias. In Small Animal Clinical Oncology. 5th edition. Edited by Withrow SJ, Vail DM, Page RL. St. Louis, MO: Elsevier; 2013:608-367.
- [12]Hori SS, Gambhir SS: Mathematical model identifies blood biomarker-based early cancer detection strategies and limitations. Sci Transl Med 2011, 3(109):109ra116.
- [13]Hu S, Vissink A, Arellano M, Roozendaal C, Zhou H, Kallenberg CG, Wong DT: Identification of autoantibody biomarkers for primary Sjogren’s syndrome using protein microarrays. Proteomic 2011, 11(8):1499-1507.
- [14]Mou Z, He Y, Wu Y: Immunoproteomics to identify tumor-associated antigens eliciting humoral response. Cancer Lett 2009, 278(2):123-129.
- [15]Stafford P, Halperin R, Legutki JB, Magee DM, Galgiani J, Johnston SA: Physical characterization of the "immunosignaturing effect". Mol Cell Proteomics 2012, 11(4):M111 011593.
- [16]AF Geijersstam V, Kibur M, Wang Z, Koskela P, Pukkala E, Schiller J, Lehtinen M, Dillner J: Stability over time of serum antibody levels to human papillomavirus type 16. J Infect Dis 1998, 177(6):1710-1714.
- [17]Chase BA, Johnston SA, Legutki JB: Evaluation of biological sample preparation for immunosignature-based diagnostics. Clin Vaccine Immunol 2012, 19(3):352-358.
- [18]Sykes KF, Legutki JB, Stafford P: Immunosignaturing: a critical review. Trends Biotechnol 2013, 31(1):45-51.
- [19]Restrepo L, Stafford P, Johnston SA: Feasibility of an early Alzheimer’s disease immunosignature diagnostic test. J Neuroimmunol 2012, 254(1-2):154-160. doi: 10.1016/j.jneuroim.2012.09.014. Epub 2012 Oct 18
- [20]Legutki JB, Johnston SA: Immunosignatures can predict vaccine efficacy. Proc Natl Acad Sci USA 2013, 110(46):18614-18619.
- [21]Hughes AK, Cichacz Z, Scheck A, Coons SW, Johnston SA, Stafford P: Immunosignaturing can detect products from molecular markers in brain cancer. PLoS One 2012, 7(7):e40201.
- [22]Johnson WE, Li C, Rabinovic A: Adjusting batch effects in microarray expression data using empirical Bayes methods. Biostatistics 2007, 8(1):118-127.
- [23]Meyer D, Dimitriadou E, Hornik K, Weingeesel A, Leisch F: e1071: Misc Functions of the Department of Statistics (e1071), TU Wien. R package version 1.6-1. 2012.
- [24]Starrak GS, Berry CR, Page RL, Johnson JL, Thrall DE: Correlation between thoracic radiographic changes and remission/survival duration in 270 dogs with lymphosarcoma. Vet Radiol Ultrasound 1997, 38(6):411-418.
- [25]Regan RC, Kaplan MS, Bailey DB: Diagnostic evaluation and treatment recommendations for dogs with substage-a high-grade multicentric lymphoma: results of a survey of veterinarians. Vet Comp Oncol 2013, 11(4):287-292.
- [26]Planinc-Peraica A, Kolonic SO, Radic-Kristo D, Dominis M, Jaksic B: Serum immunoglobulins in non-Hodgkin’s lymphoma patients. Coll Antropol 2010, 34(2):407-411.
- [27]Biggar RJ, Christiansen M, Rostgaard K, Smedby KE, Adami H-O, Glimelius B, Hjalgrim H, Melbye M: Immunoglobulin subclass levels in patients with non-Hodgkin lymphoma. Int J Cancer 2009, 124(11):2616-2620.
- [28]Marconato L, Frayssinet P, Rouquet N, Comazzi S, Leone VF, Laganga P, Rossi F, Vignoli M, Pezzoli L, Aresu L: Randomized, placebo-controlled, double-blinded chemoimmunotherapy clinical trial in a pet dog model of diffuse large B-cell lymphoma. Clin Cancer Res 2014, 20(3):668-677.
- [29]Gavazza A, Lubas G, Fridman A, Peruzzi D, Impellizeri JA, Luberto L, Marra E, Roscilli G, Ciliberto G, Aurisicchio L: Safety and efficacy of a genetic vaccine targeting telomerase plus chemotherapy for the therapy of canine B-cell lymphoma. Hum Gene Ther 2013, 24(8):728-738.
- [30]Sorenmo KU, Krick E, Coughlin CM, Overley B, Gregor TP, Vonderheide RH, Mason NJ: CD40-activated B cell cancer vaccine improves second clinical remission and survival in privately owned dogs with non-Hodgkin’s lymphoma. PLoS One 2011, 6(8):e24167.
- [31]Turek MM, Thamm DH, Mitzey A, Kurzman ID, Huelsmeyer MK, Dubielzig RR, Vail DM: Human granulocyte-macrophage colony-stimulating factor DNA cationic-lipid complexed autologous tumour cell vaccination in the treatment of canine B-cell multicentric lymphoma. Vet Comp Oncol 2007, 5(4):219-231.
- [32]Yamashita Y, Kajiura D, Tang L, Hasegawa Y, Kinoshita T, Nakamura S, Akatsuka S, Toyokuni S, Mori N: XCR1 expression and biased VH gene usage are distinct features of diffuse large B-cell lymphoma initially manifesting in the bone marrow. Am J Clin Pathol 2011, 135(4):556-564.
- [33]Warsame AA, Aasheim HC, Nustad K, Troen G, Tierens A, Wang V, Randen U, Dong HP, Heim S, Brech A, Delabie J: Splenic marginal zone lymphoma with VH1-02 gene rearrangement expresses poly- and self-reactive antibodies with similar reactivity. Blood 2011, 118(12):3331-3339.
- [34]Perez M, Pacchiarotti A, Frontani M, Pescarmona E, Caprini E, Lombardo GA, Russo G, Faraggiana T: Primary cutaneous B-cell lymphoma is associated with somatically hypermutated immunoglobulin variable genes and frequent use of VH1-69 and VH4-59 segments. Br J Dermatol 2010, 162(3):611-618.
- [35]Hashimoto T, Takishita M, Kosaka M, Sano T, Matsumoto T: Superantigens and autoantigens may be involved in the pathogenesis of gastric mucosa-associated lymphoid tissue lymphoma. Int J Hematol 2001, 74(2):197-204.
- [36]Deeb SJ, D’Souza RC, Cox J, Schmidt-Supprian M, Mann M: Super-SILAC allows classification of diffuse large B-cell lymphoma subtypes by their protein expression profiles. Mol Cell Proteomics 2012, 11(5):77-89.
- [37]Stranneheim H, Orre LM, Lehtio J, Flygare J: A comparison between protein profiles of B cell subpopulations and mantle cell lymphoma cells. Proteome Sci 2009, 7:43. BioMed Central Full Text
- [38]Felsburg PJ: Overview of immune system development in the dog: comparison with humans. Hum Exp Toxicol 2002, 21(9–10):487-492.
- [39]Manz RA, Hauser AE, Hiepe F, Radbruch A: Maintenance of serum antibody levels. Annu Rev Immunol 2005, 23:367-386.
- [40]Mumtaz IM, Hoyer BF, Panne D, Moser K, Winter O, Cheng QY, Yoshida T, Burmester G-R, Radbruch A, Manz RA, Hiepe F: Bone marrow of NZB/W mice is the major site for plasma cells resistant to dexamethasone and cyclophosphamide: Implications for the treatment of autoimmunity. J Autoimmun 2012, 39(3):180-188.
- [41]DiLillo DJ, Hamaguchi Y, Ueda Y, Yang K, Uchida J, Haas KM, Kelsoe G, Tedder TF: Maintenance of long-lived plasma cells and serological memory despite mature and memory B cell depletion during CD20 immunotherapy in mice. J Immunol 2008, 180(1):361-371.
- [42]Thalheim L, Williams LE, Borst LB, Fogle JE, Suter SE: Lymphoma immunophenotype of dogs determined by immunohistochemistry, flow cytometry, and polymerase chain reaction for antigen receptor rearrangements. J Vet Intern Med 2013, 27(6):1509-1516.
- [43]Gentilini F, Turba ME, Forni M: Retrospective monitoring of minimal residual disease using hairpin-shaped clone specific primers in B-cell lymphoma affected dogs. Vet Immunol Immunopathol 2013, 153(3–4):279-288.
- [44]Sato M, Yamzaki J, Goto-Koshino Y, Takahashi M, Fujino Y, Ohno K, Tsujimoto H: The prognostic significance of minimal residual disease in the early phases of chemotherapy in dogs with high-grade B-cell lymphoma. Vet J 2013, 195(3):319-324.
- [45]Elliott JW, Cripps P, Blackwood L: Thymidine kinase assay in canine lymphoma. Vet Comp Oncol 2013, 11(1):1-13.
- [46]Ratcliffe L, Mian S, Slater K, King H, Napolitano M, Aucoin D, Mobasheri A: Proteomic identification and profiling of canine lymphoma patients. Vet Comp Oncol 2009, 7(2):92-105.
PDF