AUTHOR=Zhang Yanli , Qin Han , Bian Jing , Ma Zhanchuan , Yi Huanfa 

TITLE=SLC2As as diagnostic markers and therapeutic targets in LUAD patients through bioinformatic analysis

JOURNAL=Frontiers in Pharmacology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2022.1045179

DOI=10.3389/fphar.2022.1045179

ISSN=1663-9812

ABSTRACT=<p>Facilitative glucose transporters (GLUTs), which are encoded by solute carrier 2A (<italic>SLC2A</italic>) genes, are responsible for mediating glucose absorption. In order to meet their higher energy demands, cancer cells are more likely than normal tissue cells to have elevated glucose transporters. Multiple pathogenic processes, such as cancer and immunological disorders, have been linked to GLUTs. Few studies, meanwhile, have been conducted on individuals with lung adenocarcinoma (LUAD) to evaluate all 14 <italic>SLC2A</italic> genes. We first identified increased protein levels of <italic>SLC2A1</italic>, <italic>SLC2A5</italic>, <italic>SLC2A6</italic>, and <italic>SLC2A9 via</italic> HPA database and downregulated mRNA levels of <italic>SLC2A3</italic>, <italic>SLC2A6</italic>, <italic>SLC2A9</italic>, and <italic>SLC2A14</italic> by ONCOMINE and UALCAN databases in patients with LUAD. Additionally, lower levels of <italic>SLC2A3</italic>, <italic>SLC2A6</italic>, <italic>SLC2A9</italic>, <italic>SLC2A12</italic>, and <italic>SLC2A14</italic> and higher levels of <italic>SLC2A1</italic>, <italic>SLC2A5</italic>, <italic>SLC2A10</italic>, and <italic>SLC2A11</italic> had an association with advanced tumor stage. <italic>SLC2A1</italic>, <italic>SLC2A7</italic>, and <italic>SLC2A11</italic> were identified as prognostic signatures for LUAD. Kaplan-Meier analysis, Univariate Cox regression, multivariate Cox regression and ROC analyses further revealed that these three genes signature was a novel and important prognostic factor. Mechanistically, the aberrant expression of these molecules was caused, in part, by the hypomethylation of <italic>SLC2A3</italic>, <italic>SLC2A10</italic>, and <italic>SLC2A14</italic> and by the hypermethylation of <italic>SLC2A1</italic>, <italic>SLC2A2</italic>, <italic>SLC2A5</italic>, <italic>SLC2A6</italic>, <italic>SLC2A7</italic>, and <italic>SLC2A11</italic>. Additionally, <italic>SLC2A3</italic>, <italic>SLC2A5</italic>, <italic>SLC2A6</italic>, <italic>SLC2A9</italic>, and <italic>SLC2A14</italic> contributed to LUAD by positively modulating M2 macrophage and T cell exhaustion. Finally, pathways involving <italic>SLC2A1</italic>/BUB1B/mitotic cell cycle, <italic>SLC2A5</italic>/CD86/negative regulation of immune system process, <italic>SLC2A6</italic>/PLEK/lymphocyte activation, <italic>SLC2A9</italic>/CD4/regulation of cytokine production might participate in the pathogenesis of LUAD. In summary, our results will provide the theoretical basis on <italic>SLC2As</italic> as diagnostic markers and therapeutic targets in LUAD.</p>