Proteomic analysis identifies galectin-1 as a predictive biomarker for relapsed/refractory disease in classical Hodgkin lymphoma

被引:75
作者
Kamper, Peter [1 ]
Ludvigsen, Maja [2 ]
Bendix, Knud [3 ]
Hamilton-Dutoit, Stephen [3 ]
Rabinovich, Gabriel A. [4 ]
Moller, Michael Boe [5 ]
Nyengaard, Jens R. [6 ]
Honore, Bent [2 ]
d'Amore, Francesco [1 ]
机构
[1] Aarhus Univ Hosp, Dept Hematol, DK-8000 Aarhus C, Denmark
[2] Aarhus Univ, Dept Med Biochem, Aarhus, Denmark
[3] Aarhus Univ Hosp, Inst Pathol, DK-8000 Aarhus C, Denmark
[4] Consejo Nacl Invest Cient & Tecn, Inst Biol & Med Expt, Lab Inmunopatol, RA-1033 Buenos Aires, DF, Argentina
[5] Odense Univ Hosp, Dept Pathol, DK-5000 Odense, Denmark
[6] Aarhus Univ Hosp, Ctr Stochast Geometry & Adv Bioimaging, Stereol & Electron Microscopy Lab, DK-8000 Aarhus C, Denmark
基金
英国医学研究理事会;
关键词
EPSTEIN-BARR-VIRUS; T-CELLS; PROTEIN IDENTIFICATION; TUMOR MICROENVIRONMENT; FOLLICULAR LYMPHOMA; MOLECULAR-FEATURES; IMMUNE PRIVILEGE; STERNBERG CELLS; MACROPHAGES; EXPRESSION;
D O I
10.1182/blood-2010-12-327346
中图分类号
R5 [内科学];
学科分类号
100201 [内科学];
摘要
Considerable effort has been spent identifying prognostic biomarkers in classic Hodgkin lymphoma (cHL). The aim of our study was to search for possible prognostic parameters in advanced-stage cHL using a proteomics-based strategy. A total of 14 cHL pretreatment tissue samples from younger, advanced-stage patients were included. Patients were grouped according to treatment response. Proteins that were differentially expressed between the groups were analyzed using 2D-PAGE and identified by liquid chromatography mass spectrometry. Selected proteins were validated using Western blot analysis. One of the differentially expressed proteins, the carbohydrate-binding protein galectin-1 (Gal-1), was further analyzed using immunohistochemistry HC and its expression was correlated with clinicopathologic and outcome parameters in 143 advanced-stage cHLcases. At the univariate level, high Gal-1 expression in the tumor microenvironment was correlated with poor event-free survival (P = .02). Among younger (<= 61 years) patients, high Gal-1 was correlated with poorer overall and event-free survival (both P = .007). In this patient group and at the multivariate level, high Gal-1 expression retained a significant predictive impact on event-free survival. Therefore, in addition to its functional role in cHL-induced immunosuppression, Gal-1 is also associated with an adverse clinical outcome in this disease. (Blood. 2011;117(24):6638-6649)
引用
收藏
页码:6638 / 6649
页数:12
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