title: Reduced expression of TRIM21/Ro52 predicts poor prognosis in diffuse large B-cell lymphoma patients with and without rheumatic disease.
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.
  
  
  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.
authors.affiliation: Unit of Experimental Rheumatology, Department of Medicine, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
authors.forename: S
authors.initials: S
authors.lastname: Brauner
authors.affiliation: Unit of Experimental Rheumatology, Department of Medicine, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
authors.forename: W
authors.initials: W
authors.lastname: Zhou
authors.affiliation: Unit of Rheumatology, Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
authors.forename: C
authors.initials: C
authors.lastname: Backlin
authors.affiliation: Institute of Clinical Research, University of Southern Denmark, Odense, Denmark.|Odense University Hospital, Odense, Denmark.
authors.forename: T M
authors.initials: TM
authors.lastname: Green
authors.affiliation: Unit of Experimental Rheumatology, Department of Medicine, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
authors.forename: L
authors.initials: L
authors.lastname: Folkersen
authors.affiliation: Unit of Experimental Rheumatology, Department of Medicine, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
authors.forename: M
authors.initials: M
authors.lastname: Ivanchenko
authors.affiliation: Rheumatology Clinic, Malar Hospital, Eskilstuna, Sweden.
authors.forename: B
authors.initials: B
authors.lastname: Löfström
authors.affiliation: Department of Hematopathology, University of Texas, MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Z Y
authors.initials: ZY
authors.lastname: Xu-Monette
authors.affiliation: Department of Hematopathology, University of Texas, MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: K H
authors.initials: KH
authors.lastname: Young
authors.affiliation: Odense University Hospital, Odense, Denmark.
authors.forename: L
authors.initials: L
authors.lastname: Møller Pedersen
authors.affiliation: Institute of Clinical Research, University of Southern Denmark, Odense, Denmark.|Odense University Hospital, Odense, Denmark.
authors.forename: M
authors.initials: M
authors.lastname: Boe Møller
authors.affiliation: Department of Immunology, Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden.
authors.forename: C
authors.initials: C
authors.lastname: Sundström
authors.affiliation: Unit of Oncology, Department of Radiology, Oncology and Radiation Sciences, Uppsala University, Uppsala, Sweden.
authors.forename: G
authors.initials: G
authors.lastname: Enblad
authors.affiliation: Unit of Rheumatology, Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
authors.forename: E
authors.initials: E
authors.lastname: Baecklund
authors.affiliation: Unit of Experimental Rheumatology, Department of Medicine, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
authors.forename: M
authors.initials: M
authors.lastname: Wahren-Herlenius
mesh_terms: D000368:Aged; D058846:Antibodies, Monoclonal, Murine-Derived / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D015415:Biomarkers / Q000032:analysis*; D002478:Cells, Cultured; D003520:Cyclophosphamide / Q000627:therapeutic use; D004317:Doxorubicin / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy / Q000401:mortality*; D008297:Male; D011239:Prednisolone / Q000627:therapeutic use; D011241:Prednisone / Q000627:therapeutic use; D011379:Prognosis; D060888:Real-Time Polymerase Chain Reaction; D012216:Rheumatic Diseases / Q000150:complications*; D012261:Ribonucleoproteins / Q000032:analysis*; D000069283:Rituximab; D014750:Vincristine / Q000627:therapeutic use; D000099207:SS-A Antigen
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D015415:Biomarkers; D003520:Cyclophosphamide; D004317:Doxorubicin; D011239:Prednisolone; D011241:Prednisone; D012261:Ribonucleoproteins; D000069283:Rituximab; D014750:Vincristine; D000099207:SS-A Antigen; C571759:R-CHOP protocol
keywords: Ro52; TRIM21; biomarker; diffuse large B-cell lymphoma; prognosis