The definition of the gene expression profile of genes encoding Ion Channels and Transporters (ICT-GEP) represents a novel and attracting aspect in cancer. We determined the ICT-GEP of Follicular Lymphoma (FL), and compared it with that of the more aggressive Diffuse Large B Cell Lymphoma (DLBCL). cDNA microarray data were collected both from patients enrolled for this study, and from public datasets. In FL the ICT-GEP indicated the overexpression of both the K
+
channel encoding gene
KCNN4
, and
SLC2A1
, which encodes the Glut1 glucose transporter.
SLC2A1
turned out to represent the hub of a functional network, connecting channels and transporters in FL. Relapsed FL patients were characterised by 38 differentially expressed ICT genes, among which
ATP9A
,
SLC2A1
and
KCNN4
were under-expressed, indicating a down-regulation of both excitability and glycolysis. A completely different profile of K
+
channel encoding genes emerged in DLBCL accompanied by the over-expression of the fatty acid transporter-encoding gene
SLC27A1
as well as of the metabolism regulator
NCoR1
. This indicates a change in excitability and a shift towards an oxidative metabolism in DLBCL. Overall, the ICT-GEP may contribute to identifying novel lymphoma biomarkers related to excitability and metabolic pathways, with particular relevance for drug resistant, relapsed FL.