Abstract
BACKGROUND: The treatment of lung adenocarcinoma (LUAD) has been stuck in a bottleneck due to a number of factors. There is a pressing need for research into potential genetic markers to help drug development and improve the prognosis of patients. SLC2A1 has been reported in multiple LUAD-related prognosis prediction signatures. However, the role of SLC2A1 in the occurrence and development of LUAD and its impact on prognosis remain elusive. METHODS: The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) were used to acquire the samples. We used R to perform statistical analysis, Gene Set Enrichment Analysis (GSEA), immune infiltration and immune cell correlation analysis, drug sensitivity analysis, and visualization. The immune cell score was calculated using the Timer2.0 database. Prognostic analysis was performed using R, Gene Expression Profiling Interactive Analysis (GEPIA), and the Kaplan-Meier Plotter. Overall survival and progression free survival were the main outcome of prognosis analysis. Protein-protein interaction, disease-genetics analysis, and tissue-specific enrichment analyses were performed using Metascape. RESULTS: SLC2A1 was highly expressed in LUAD tissues. Univariate COX regression [hazard ratio (HR) =1.689, 95% confidence interval (CI): 1.242-2.249, P<0.001] and multivariate COX regression including age, gender, smoking, TNM stage and SLC2A1 expression (HR =1.567, 95% CI: 1.127-2.179, P=0.008) showed that SLC2A1 was an independent prognostic risk factor for LUAD. GSEA and Metascape analysis showed that SLC2A1 was strongly associated with the cell cycle, mitosis, lung tissue, and tumor recurrence. Immune correlation analysis showed that SLC2A1 was associated with two tumor infiltration immune cells: activated CD (cluster of differentiation)4(+) memory T cells (r=0.31, P=0.003) and activated mast cells (r=-0.28, P=0.010). Moreover, patients with high SLC2A1 expression had higher immune checkpoint molecules and Tumor Immune Dysfunction and Exclusion (TIDE) scores, indicating poorer immunotherapy efficacy. Patients with high SLC2A1 expression were more sensitive to chemotherapy drugs and less sensitive to targeted drugs compared to those with low SLC2A1 expression. CONCLUSIONS: The high expression of SLC2A1 in LUAD predicted poor prognosis and was closely related to tumor immunity, which could be used as an effective prognostic biomarker to provide a new strategy for clinical prognosis assessment and immunotherapy for LUAD.