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Sphingosine‐1‐phosphate receptor 1 as a prognostic biomarker and therapeutic target for patients with primary testicular diffuse large B‐cell lymphoma
Author(s) -
Koresawa Risa,
Yamazaki Kazuto,
Oka Daigo,
Fujiwara Hideyo,
Nishimura Hirotake,
Akiyama Takashi,
Hamasaki Shuji,
Wada Hideho,
Sugihara Takashi,
Sadahira Yoshito
Publication year - 2016
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/bjh.14054
Subject(s) - s1pr1 , diffuse large b cell lymphoma , sphingosine , sphingosine 1 phosphate receptor , cancer research , lymphoma , sphingosine kinase , sphingosine 1 phosphate , biology , sphingolipid , immunohistochemistry , pathology , receptor , medicine , microbiology and biotechnology , vascular endothelial growth factor a , vascular endothelial growth factor , vegf receptors
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 (S1 PR 1) 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 S1 PR 1 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 S1 PR 1 overexpression in 15·7% of all cases with DLBCL and in 54·2% of 24 cases with primary testicular ( PT )‐ DLBCL ; S1 PR 1 expression correlated with S1 PR 1 mRNA expression and STAT 3 phosphorylation in fresh samples. Analyses of data from a single institution suggested that S1 PR 1 overexpression was an independent negative prognostic marker in 68 patients with DLBCL of clinical stages I and II . The present high prevalence of S1 PR 1 overexpression warrants the consideration of PT ‐ DLBCL as a distinct disease subtype and suggests the potential of the S1P/S1 PR 1 axis as a therapeutic target.