Construction of a ubiquitination-related gene signature to predict prognosis and treatment response in lung adenocarcinoma

Abstract

Background & Objective: The prognosis of lung adenocarcinoma (LUAD) remains poor, primarily due to treatment resistance and a lack of effective biomarkers. This research investigated the potential of ubiquitination-related genes (UbRG) as prognostic indicators for LUAD.

Methodology: This study was conducted at Tianjin Medical University Cancer Institute and Hospital from May 2025 to October 2025. Leveraging data from TCGA, we initially employed WGCNA to identify key modules of UbRG associated with LUAD. Then, a multigene prognostic signature was developed. To investigate the mechanisms, GSEA and CIBERSORT were used to detect activated signaling pathways and immune landscape, respectively. Finally, drug sensitivity analysis was performed.

Results: Our analysis identified nine gene pairs that constitute the UbRG prognostic signature, with individuals in the high-risk cohort generally experiencing worse outcomes. Pathway enrichment analyses revealed immune response pathways in the low-risk cohort and the cell cycle and DNA replication pathways in the high-risk cohort. CIBERSORT revealed distinct immune cell distributions, with more CD4+ T cells and DCs in the low-risk cohort. Drug sensitivity analysis suggest that the low-risk group may exhibit a greater sensitivity to both chemotherapy and targeted treatments.

Conclusion: This study presents a novel UbRG signature for LUAD prognosis, emphasizing the role of ubiquitination in the immune response. These findings may guide future therapeutic strategies in LUAD.