Differential Expression of RanGAP1 between Reactive and Neoplastic B-Cell Proliferations: Using Comparative Proteomics to Search Lymphoma Biomarker and Its Clinicopathologic Role.
Kung-Chao Chang, Hsiang-Lin Song, Chien-Hun Huang, Chen Chang, Ying-Tai Jin. National Cheng Kung University and Hospital, Tainan, Taiwan; Taiwan Adventist Hospital, Taipei, Taiwan
Background: Tumor biomarkers play a pivotal role in screening, diagnosis, and follow-up of disease. Lymphoma markers may also contribute to treatment strategy, prognostic stratification, and study of tumorigenesis. Diffuse large B-cell lymphoma (DLBCL), the most common subtype of non-Hodgkin lymphomas, accounts for 30% to 40% of all lymphoma cases. However, long-term survival by current chemotherapy was achieved in only 40% of patients, warranting the development of novel therapeutic strategies. Of them, immunotherapy is the most promising. Thus, the lymphoma-specific biomarkers (lymphoma-specific antigens) can also serve as the targets for the immunotherapy.
Design: By comparative proteomics analysis of two DLBCL cell lines with a lymphoblastoid cell line (LCL), we found RanGAP1 (Ran GTPase-activating protein 1) differentially expressed between DLBCL and B-cell hyperplasia that was validated on immunoblotting.
Results: In addition, immunostaining showed that the majority of DLBCLs (92%, 46/50) were RanGAP1-positive, in contrast to reactive lymphoid hyperplasia (n=12), which revealed RanGAP1 positivity only in germinal center cells. Interestingly, serum level of RanGAP1 was also higher in DLBCL patients (n = 50) than normal populations (n = 36)(3.83 ± 2.76 ng/mL vs. 2.43 ± 1.98 ng/mL, p = 0.0074). For other B-cell lymphomas, RanGAP1 was frequently expressed in tumors with brisk mitotic activity (B-lymphoblastic lymphoma/leukemia, 93.3% and Burkitt lymphoma, 94.6%) or with cell cycle aberrations (mantle cell lymphoma, 83.3% and Hodgkin lymphoma, 90.5%).
|Lymphoma types||No.||Positivity||(%)||M/F||Age (mean)|
|Small lymphocytic lymphoma||16||1/16||6.3%||12/4||64.9|
|Mantle cell lymphoma||12||10/12||83.3%||11/1||67.3|
|Marginal zone lymphoma, MALT type||30||5/30||16.7%||13/17||60.1|