The role of SLC2A1 in lung adenocarcinoma: From tumorigenesis to patient survival.

OBJECTIVE

Our study aimed at systematically exploring the effect of the solute carrier family 2 Member (SLC2A) genes family on the prognosis and immune landscape of lung adenocarcinoma (LUAD) patients. Furthermore, we sought to determine the SLC2A1 function in LUAD initiation and progression through in vivo and in vitro experiments.

METHODS

A comprehensive bioinformatics analysis was conducted utilizing online tools and software, including R packages, Gene Set Cancer Analysis (GSCA), cBio Cancer Genomics Portal (cBioPortal), GeneMANIA, STRING, and Xiantao Academic Online databases, to assess the functional implications of the SLC2A gene family in LUAD. Concurrently, in vivo and in vitro experiments at the cellular and animal levels were conducted to ascertain the effects of SLC2A1 gene knockout on LUAD development.

RESULTS

Compared to normal tissues, the SLC2A gene family exhibited significant upregulation across various tumor types, including LUAD, with a low mutation frequency in LUAD. SLC2A1 and SLC2A7 emerged as prognostic biomarkers for LUAD. The receiver operating characteristic (ROC) curve analysis revealed high diagnostic accuracy of SLC2A1 for LUAD. A significant negative correlation was observed between SLC2A1 expression and DNA methylation levels in LUAD, and the gene was closely linked to cellular processes such as cell nuclear division, DNA replication, and metabolism. Moreover, SLC2A1 expression was strongly linked to immune infiltration and regulation across different tumor types. In vitro and in vivo experiments showcased that SLC2A1 inhibition significantly hampered LUAD A549 cell proliferation, migration, and invasion capabilities, as well as tumor growth in nude mice. Finally, our study demonstrated that reduced SLC2A1 expression influenced the expression of molecules within the P53 signaling pathway.

CONCLUSIONS

This study elucidates the functional role of the SLC2A gene family in the pathogenesis of LUAD, underscoring the importance of SLC2A1 in LUAD diagnosis, prognosis, and immune response, and presenting SLC2A1 as a promising biomarker for LUAD.