title: Sphingosine-1-phosphate receptor 1 as a prognostic biomarker and therapeutic target for patients with primary testicular diffuse large B-cell lymphoma.
abstract: Sphingosine-1-phosphate (S1P) is a potent lipid mediator that is produced during the metabolism of sphingolipid by sphingosine kinase. S1P has been implicated in the migration and trafficking of lymphocytes and several lymphoid malignancies through S1P receptors. Moreover, the overexpression of sphingosine-1-phosphate receptor 1 (S1PR1) has been correlated with the constitutive activation of signal transducer and activator of transcription (STAT)3 and poor prognosis of diffuse large B-cell lymphoma (DLBCL). Thus, in this study, we examined the expression of S1PR1 in 198 DLBCL samples collected from nodal and various extranodal sites and sub-classified formalin-fixed paraffin-embedded tissue samples into germinal centre B-cell-like (GCB) and non-GCB subgroups using immunohistochemistry. These analyses showed S1PR1 overexpression in 15·7% of all cases with DLBCL and in 54·2% of 24 cases with primary testicular (PT)-DLBCL; S1PR1 expression correlated with S1PR1mRNA expression and STAT3 phosphorylation in fresh samples. Analyses of data from a single institution suggested that S1PR1 overexpression was an independent negative prognostic marker in 68 patients with DLBCL of clinical stages I and II. The present high prevalence of S1PR1 overexpression warrants the consideration of PT-DLBCL as a distinct disease subtype and suggests the potential of the S1P/S1PR1 axis as a therapeutic target.
authors.affiliation: Department of Pathology, Kawasaki Medical School, Kurashiki, Japan.
authors.forename: Risa
authors.initials: R
authors.lastname: Koresawa
authors.affiliation: Department of Pathology, Teikyo University, Chiba Medical Centre, Ichihara, Japan.
authors.forename: Kazuto
authors.initials: K
authors.lastname: Yamazaki
authors.affiliation: Department of Pathology, Kawasaki Medical School, Kurashiki, Japan.
authors.forename: Daigo
authors.initials: D
authors.lastname: Oka
authors.affiliation: Department of Pathology, Kawasaki Medical School, Kurashiki, Japan.
authors.forename: Hideyo
authors.initials: H
authors.lastname: Fujiwara
authors.affiliation: Department of Pathology, Kawasaki Medical School, Kurashiki, Japan.
authors.forename: Hirotake
authors.initials: H
authors.lastname: Nishimura
authors.affiliation: Department of Pathology, Kawasaki Medical School, Kurashiki, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Akiyama
authors.affiliation: Department of Pathology, Kawasaki Medical School, Kurashiki, Japan.
authors.forename: Shuji
authors.initials: S
authors.lastname: Hamasaki
authors.affiliation: Department of Haematology, Kawasaki Medical School, Kurashiki, Japan.
authors.forename: Hideho
authors.initials: H
authors.lastname: Wada
authors.affiliation: Department of Haematology, Kawasaki Medical School, Kurashiki, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Sugihara
authors.affiliation: Department of Pathology, Kawasaki Medical School, Kurashiki, Japan.
authors.forename: Yoshito
authors.initials: Y
authors.lastname: Sadahira
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000032:analysis; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D018858:Germinal Center; D006801:Humans; D007150:Immunohistochemistry; D016403:Lymphoma, Large B-Cell, Diffuse / Q000737:chemistry / Q000175:diagnosis*; D008246:Lysophospholipids; D008297:Male; D008875:Middle Aged; D010766:Phosphorylation; D011379:Prognosis; D012333:RNA, Messenger / Q000032:analysis; D049349:Receptors, Lysosphingolipid / Q000032:analysis* / Q000235:genetics; D050796:STAT3 Transcription Factor / Q000378:metabolism; D013110:Sphingosine / Q000031:analogs & derivatives; D013736:Testicular Neoplasms
chemical_list: D015415:Biomarkers; D008246:Lysophospholipids; D012333:RNA, Messenger; D049349:Receptors, Lysosphingolipid; D050796:STAT3 Transcription Factor; C060506:sphingosine 1-phosphate; D013110:Sphingosine
keywords: STAT3; diffuse large B-cell lymphoma; immunohistochemistry; primary testicular lymphoma; sphingosine-1-phosphate receptor 1