Oncotarget

Research Papers:

VEGF121, is predictor for survival in activated B-cell-like diffuse large B-cell lymphoma and is related to an immune response gene signature conserved in cancers

Julien Broséus, Samia Mourah, Gérard Ramstein, Sophie Bernard, Nicolas Mounier, Wendy Cuccuini, Philippe Gaulard, Christian Gisselbrecht, Josette Brière, Rémi Houlgatte and Catherine Thieblemont _

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Oncotarget. 2017; 8:90808-90824. https://doi.org/10.18632/oncotarget.19385

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Abstract

Julien Broséus1,2,*, Samia Mourah3,4,5,*, Gérard Ramstein6, Sophie Bernard7, Nicolas Mounier8, Wendy Cuccuini9, Philippe Gaulard10,11, Christian Gisselbrecht7,12, Josette Brière13, Rémi Houlgatte1,14,** and Catherine Thieblemont3,7

1 Inserm U954, Faculty of Medicine, University of Lorraine, Nancy, France

2 University Hospital of Nancy, Hematology Laboratory, Nancy, France

3 Paris Diderot University, Sorbonne Paris Cité, Paris, France

4 APHP, Saint Louis University Hospital, Pharmacology-Biologic Laboratory, Paris, France

5 Inserm UMRS 976, France

6 LS2N - DUKe, University of Nantes, Nantes, France

7 APHP, Saint-Louis University Hospital, Hemato-Oncology, Paris, France

8 University Hospital of L’archet, Nice, France

9 APHP, Saint-Louis University Hospital, Hematology Laboratory, Paris, France

10 Department of Pathology, APHP, Henri Mondor University Hospital, Creteil, France

11 Inserm U955, University Paris-Est, Créteil, France

12 Lymphoma Study Association, Pierre-Bénite, France

13 Department of Pathology, APHP, Saint-Louis University Hospital, Paris, France

14 University Hospital of Nancy, DRCI, Nancy, France

* Julien Broséus and Samia Mourah have contributed equally to this work

** Catherine Thieblemont and Rémi Houlgatte have contributed equally to this work

Correspondence to:

Catherine Thieblemont, email:

Rémi Houlgatte, email:

Keywords: ABC, like DLBCL, angiogenesis, immune response, cancer

Received: June 12, 2017 Accepted: July 03, 2017 Published: July 19, 2017

Abstract

Tumor microenvironment including endothelial and immune cells plays a crucial role in tumor progression and has been shown to dramatically influence cancer survival. In this study, we investigated the clinical relevance of the gene expression of key mediators of angiogenesis, VEGF isoforms 121, 165, and 189, and their receptors (VEGFR-1 and R-2) in a cohort of patients (n = 37) with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) from the Collaborative Trial in Relapsed Aggressive Lymphoma (CORAL). In patients with ABC-like DLBCL, but not in patients with GCB-like DLBCL, low VEGF121 expression was associated with a significantly better survival than in those with high VEGF121 level: 4-year overall survival at 100% vs 36% (p = .011), respectively. A specific gene signature including 57 genes was correlated to VEGF121 expression level and was analyzed using a discovery process in 1,842 GSE datasets of public microarray studies. This gene signature was significantly expressed in other cancer datasets and was associated with immune response. In conclusion, low VEGF121 expression level was significantly associated with a good prognosis in relapsed/refractory ABC-like DLBCL, and with a well-conserved gene-expression profiling signature related to immune response. These findings pave the way for rationalization of drugs targeting immune response in refractory/relapsed ABC-like DLBCL.


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PII: 19385