Abstract
Introduction: Lung adenocarcinoma (LUAD) is a global health threat due to its rapid malignant progression and poor prognosis. Ferroptosis plays a key role in LAUD progression, but the critical ferroptosis-related factors in LUAD have not been further explored. The aim of this work was to explore novel ferroptosis-related therapeutic targets and prognostic biomarkers for LUAD. Methods: Using TCGA and GEO datasets of LAUD samples, we constructed a ferroptosis risk model and identified SDCBP2 as a LUAD hub gene. The TCGA data and single-cell database indicated that SDCBP2 was overexpressed in LUAD and significantly enriched in malignant cells. Subsequently, bioinformatics analysis, functional studies, and clinical samples were employed to assess the prognostic value and role of SDCBP2. Results: The multivariate Cox regression confirmed SDCBP2 as an independent prognostic factor. The ROC curve based on SDCBP2 expression showed a strong predictive power for the prognosis of LUAD patients at 1, 3, and 5 years. The GSEA and GO/KEGG analysis linked SDCBP2 to ferroptosis and cell cycle pathways. Next, the in vitro results revealed that knockdown of SDCBP2 induced G0/G1 phase arrest and apoptosis, and inhibited the proliferation and migration of LUAD cells. Meanwhile, knockdown of SDCBP2 reduced glutathione (GSH) levels and enhanced the cellular level of ROS. Furthermore, we found a correlation between the expression of SDCBP2 and SLC7A11, and patients with concurrent high expression of both exhibited a poorer prognosis, although the regulatory relationship between the two genes remains to be further investigated. Discussion: This study demonstrates that SDCBP2 promotes tumor progression and is a novel ferroptosis-related prognostic biomarker for LUAD.