title: Expressions of SH3BP5, LMO3, and SNAP25 in diffuse large B-cell lymphoma cells and their association with clinical features.
abstract: Diffuse large B-cell lymphoma (DLBCL) is clinicopathologically and genetically heterogeneous with variable clinical outcomes. We previously identified signature genes overexpressed in CD5-positive (CD5(+) ) DLBCL, which is a poor prognostic subgroup of DLBCL. To elucidate the clinical significance of the protein expression of the signature genes overexpressed in CD5(+) DLBCL with regard to all DLBCL, not otherwise specified (NOS), 10 genes (SH3BP5, LMO3, SNAP25, SYT5, SV2C, CABP1, FGF1, FGFR2, NEUROD1, and SYN2) were selected and examined immunohistochemically with samples from 28 patients with DLBCL, NOS. Only three protein expressions, SH3BP5, LMO3, and SNAP25, were detected in DLBCL cells and then analyzed further with samples from 187 patients with DLBCL, NOS. The SH3BP5, LMO3, and SNAP25 proteins were expressed in 60% (103/173), 34% (59/175), and 46% (77/168) of DLBCL patients, respectively. These protein expressions were associated with CD5 expression, and only SH3BP5 was frequently expressed in activated B-cell-like DLBCL (P = 0.046). Compared to the SH3BP5-negative group, the SH3BP5(+) group was correlated with elderly onset (>60 years, P = 0.0096) and advanced-stage disease (stage III/IV, P = 0.037). The LMO3(+) group showed a worse performance status (>1, P = 0.0004). The SH3BP5(+) group and the LMO3(+) group had significantly worse overall survival than the negative groups (P = 0.030, 0.034; respectively) for the entire group. In a subgroup analysis of patients treated with rituximab-containing chemotherapy, there was no significant difference between groups. To the best of our knowledge, this is the first report showing the protein expressions of SH3BP5, LMO3, and SNAP25 in DLBCL cells and their clinical significance in patients with DLBCL. The SH3BP5 and LMO3 protein expressions are associated with the baseline clinical characteristics of DLBCL.
authors.affiliation: Department of Hematology and Oncology, Mie University Graduate School of Medicine, Tsu, Japan.
authors.forename: Kyoko
authors.initials: K
authors.lastname: Kobayashi
authors.affiliation: Department of Hematology and Oncology, Mie University Graduate School of Medicine, Tsu, Japan.
authors.forename: Motoko
authors.initials: M
authors.lastname: Yamaguchi
authors.affiliation: Department of Hematology and Oncology, Mie University Graduate School of Medicine, Tsu, Japan.
authors.forename: Kana
authors.initials: K
authors.lastname: Miyazaki
authors.affiliation: Pathology Division, Mie University Hospital, Tsu, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Imai
authors.affiliation: Mie University School of Medicine, Tsu, Japan.
authors.forename: Kaori
authors.initials: K
authors.lastname: Yokoe
authors.affiliation: Department of Microbiology and Molecular Genetics, Mie University Graduate School of Medicine, Tsu, Japan.
authors.forename: Ryoichi
authors.initials: R
authors.lastname: Ono
authors.affiliation: Department of Microbiology and Molecular Genetics, Mie University Graduate School of Medicine, Tsu, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Nosaka
authors.affiliation: Department of Hematology and Oncology, Mie University Graduate School of Medicine, Tsu, Japan.
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Katayama
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000378:metabolism; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D006801:Humans; D053208:Kaplan-Meier Estimate; D060588:LIM Domain Proteins / Q000378:metabolism; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism*; D009367:Neoplasm Staging; D011379:Prognosis; D050825:Synaptosomal-Associated Protein 25 / Q000378:metabolism; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D060588:LIM Domain Proteins; C502335:LMO3 protein, human; D009363:Neoplasm Proteins; C112230:SH3BP5 protein, human; C494208:SNAP25 protein, human; D050825:Synaptosomal-Associated Protein 25
keywords: CD5; LMO3; SH3BP5; SNAP25; diffuse large B-cell lymphoma