Distinct Gene Expression Patterns of Calcium Channels and Related Signaling Pathways Discovered in Lymphomas.

Cell surface calcium (Ca) channels permit Ca ion influx, with Ca taking part in cellular functions such as proliferation, survival, and activation. The expression of voltage-dependent Ca (Ca) channels may modulate the growth of hematologic cancers. Profile analysis of Ca channels, with a focus on the Ca release-activated Ca (CRAC) and L-type Ca channels, was performed on RNA sequencing data from lymphoma cell lines and samples derived from patients with diffuse large B cell lymphoma (DLBCL). Ca1.2 expression was found to be elevated in classical Hodgkin lymphoma (CHL) cell lines when compared to other B cell lymphoma cell lines. In contrast, CHL exhibited reduced expression of ORAI2 and STIM2. In our differential expression analysis comparing activated B cell-like DLBCL (ABC-DLBCL) and germinal centre B cell-like DLBCL (GCB-DLBCL) patient samples, ABC-DLBCL revealed stronger expression of Ca1.3, whereas Ca1.1, Ca1.2, and Ca1.4 showed greater expression levels in GCB-DLBCL. Interestingly, no differences in ORAI/STIM expression were noted in the patient samples. As Ca is known to bind to calmodulin, leading to calcineurin activation and the passage of nuclear factor of activated T cells (NFAT) to the cell nucleus, pathways for calcineurin, calmodulin, NFAT, and Ca signaling were also analyzed by gene set enrichment analysis. The NFAT and Ca signaling pathways were found to be upregulated in the CHL cell lines relative to other B cell lymphoma cell lines. Furthermore, the calmodulin and Ca signaling pathways were shown to be downregulated in the ABC-DLBCL patient samples. The findings of this study suggest that L-type Ca channels and Ca-related pathways could serve as differentiating components for biologic therapies in targeted lymphoma treatments.