S Brauner1, W Zhou1, C Backlin2, T M Green3,4, L Folkersen1, M Ivanchenko1, B Löfström5, Z Y Xu-Monette6, K H Young6, L Møller Pedersen4, M Boe Møller3,4, C Sundström7, G Enblad8, E Baecklund2, M Wahren-Herlenius1. 1. Unit of Experimental Rheumatology, Department of Medicine, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden. 2. Unit of Rheumatology, Department of Medical Sciences, Uppsala University, Uppsala, Sweden. 3. Institute of Clinical Research, University of Southern Denmark, Odense, Denmark. 4. Odense University Hospital, Odense, Denmark. 5. Rheumatology Clinic, Malar Hospital, Eskilstuna, Sweden. 6. Department of Hematopathology, University of Texas, MD Anderson Cancer Center, Houston, TX, USA. 7. Department of Immunology, Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden. 8. Unit of Oncology, Department of Radiology, Oncology and Radiation Sciences, Uppsala University, Uppsala, Sweden.
Abstract
OBJECTIVE: TRIM21 (also known as Ro52) is an autoantigen in rheumatic disease and is predominantly expressed in leucocytes. Overexpression is associated with decreased proliferation, and the TRIM21 gene maps to a tumour suppressor locus. We therefore investigated the expression of TRIM21 in patients with diffuse large B-cell lymphoma (DLBCL) and its potential usefulness as a prognostic biomarker. MATERIALS AND METHODS: TRIM21 expression levels were assessed by immunohistochemistry in lymphoma biopsies from three cohorts of patients with DLBCL: 42 patients with rheumatic disease treated with a cyclophosphamide, vincristine, doxorubicin and prednisone (CHOP)-like regimen, 76 CHOP-treated and 196 rituximab-CHOP-treated nonrheumatic patients. Expression was correlated with clinical and biomedical parameters. TRIM21 expression was assessed in relation to lymphocyte proliferation by quantitative PCR and correlated with (3) H-thymidine incorporation and propidium iodine staining. RESULTS: TRIM21 expression levels differed in the lymphomas compared to normal lymphoid tissue, with reduced expression correlating with shorter overall survival in all three cohorts. In the two larger cohorts, progression-free survival was assessed and was also found to correlate with TRIM21 expression. The association was independent of commonly used clinical prognostic scores, lymphoma subtype and several previously reported prognostic biomarkers. In agreement with this clinical observation, we noted an inverse correlation between TRIM21 expression and proliferation of leucocytes in vitro. CONCLUSIONS: We show that loss of TRIM21 expression is associated with more aggressive lymphoma and increased proliferation, whereas maintenance of TRIM21 expression is associated with better prognosis in patients with DLBCL. Based on our findings, we suggest that TRIM21 should be considered as a novel biomarker for lymphoma characterization and for predicting patient survival.
OBJECTIVE:TRIM21 (also known as Ro52) is an autoantigen in rheumatic disease and is predominantly expressed in leucocytes. Overexpression is associated with decreased proliferation, and the TRIM21 gene maps to a tumour suppressor locus. We therefore investigated the expression of TRIM21 in patients with diffuse large B-cell lymphoma (DLBCL) and its potential usefulness as a prognostic biomarker. MATERIALS AND METHODS:TRIM21 expression levels were assessed by immunohistochemistry in lymphoma biopsies from three cohorts of patients with DLBCL: 42 patients with rheumatic disease treated with a cyclophosphamide, vincristine, doxorubicin and prednisone (CHOP)-like regimen, 76 CHOP-treated and 196 rituximab-CHOP-treated nonrheumaticpatients. Expression was correlated with clinical and biomedical parameters. TRIM21 expression was assessed in relation to lymphocyte proliferation by quantitative PCR and correlated with (3) H-thymidine incorporation and propidium iodine staining. RESULTS:TRIM21 expression levels differed in the lymphomas compared to normal lymphoid tissue, with reduced expression correlating with shorter overall survival in all three cohorts. In the two larger cohorts, progression-free survival was assessed and was also found to correlate with TRIM21 expression. The association was independent of commonly used clinical prognostic scores, lymphoma subtype and several previously reported prognostic biomarkers. In agreement with this clinical observation, we noted an inverse correlation between TRIM21 expression and proliferation of leucocytes in vitro. CONCLUSIONS: We show that loss of TRIM21 expression is associated with more aggressive lymphoma and increased proliferation, whereas maintenance of TRIM21 expression is associated with better prognosis in patients with DLBCL. Based on our findings, we suggest that TRIM21 should be considered as a novel biomarker for lymphoma characterization and for predicting patient survival.
Authors: Ji-An Pan; Yu Sun; Ya-Ping Jiang; Alex J Bott; Nadia Jaber; Zhixun Dou; Bin Yang; Juei-Suei Chen; Joseph M Catanzaro; Chunying Du; Wen-Xing Ding; Maria T Diaz-Meco; Jorge Moscat; Keiko Ozato; Richard Z Lin; Wei-Xing Zong Journal: Mol Cell Date: 2016-03-03 Impact factor: 17.970