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.

journal_name

Br J Haematol

authors

Koresawa R,Yamazaki K,Oka D,Fujiwara H,Nishimura H,Akiyama T,Hamasaki S,Wada H,Sugihara T,Sadahira Y

doi

10.1111/bjh.14054

subject

Has Abstract

pub_date

2016-07-01 00:00:00

pages

264-74

issue

2

eissn

0007-1048

issn

1365-2141

journal_volume

174

pub_type

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