Expression profiling analysis of the CD5⁺ diffuse large B-cell lymphoma subgroup: Development of a CD5 signature

Diffuse large B-cell lymphoma (DLBCL) accounts for 30%of non-Hodgkin's lymphomas and is known to comprise heterogeneous groups. We previously reported that CD5 ⁺ DLBCL is a clinically distinct subgroup of these tumors that is associated with poor prognosis. In our current study, we have used gene expression profiling technology in an attempt to identify new markers and to further characterize the biological features of CD5⁺ DLBCL. Candidate genes, which showed the greatest difference in expression between 22 CD5⁺ and 26 CD5^- DLBCL cases, were selected from our screening and subjected to clustering analysis. This resulted in identification of a specific mRNA profile (a CD5 signature) for CD5⁺ DLBCL. The CD5 signature included downregulated extracellular matrix genes such as POSTN, SPARC, COL1A1, COL3A1, CTSK, MMP9 and LAMB3, and comprised upregulated genes including TRPM4. We tested this CD5 signature for its potential use as a relevant marker for CD5⁺ DLBCL and found that it did indeed recognize this subgroup. The tumors identified by the CD5 signature contained most of the CD5⁺ DLBCL cases and some CD5^- DLBCL cases. Moreover, the subgroup of cases with this CD5 signature showed a poorer prognosis. The subsequent application of the CD5 signature to the analysis of an independent series of DLBCL microarray data resulted in identification of a subgroup of DLBCL cases with a similar clinical outcome, further suggesting that the CD5 signature can be used as a clinically relevant marker of this disease.