Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.
Department of Information Engineering, University of Florence, Florence, Italy.
Sci Rep. 2019 Jun 13;9(1):8586. doi: 10.1038/s41598-019-44661-x.
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.
编码离子通道和转运蛋白(ICT-GEP)的基因表达谱的定义代表了癌症研究中一个新颖且引人注目的方面。我们确定了滤泡性淋巴瘤(FL)的 ICT-GEP,并将其与侵袭性更强的弥漫性大 B 细胞淋巴瘤(DLBCL)进行了比较。本研究从入组患者和公共数据集收集了 cDNA 微阵列数据。在 FL 中,ICT-GEP 表明编码 K 通道的基因 KCNN4 和编码葡萄糖转运蛋白 Glut1 的 SLC2A1 的过度表达。SLC2A1 最终成为 FL 中功能网络的枢纽,连接着通道和转运蛋白。复发的 FL 患者的 38 个差异表达的 ICT 基因特征,其中 ATP9A、SLC2A1 和 KCNN4 表达下调,表明兴奋性和糖酵解均下调。在 DLBCL 中出现了完全不同的 K 通道编码基因谱,同时还表达了脂肪酸转运蛋白编码基因 SLC27A1 和代谢调节剂 NCoR1。这表明 DLBCL 中的兴奋性发生变化,代谢途径向氧化代谢转变。总的来说,ICT-GEP 可能有助于确定与兴奋性和代谢途径相关的新型淋巴瘤生物标志物,对于耐药、复发的 FL 具有特别重要的意义。