Abstract
Lung squamous cell carcinoma (LUSC), a major subtype of non-small cell lung cancer, remains challenging to treat due to poor prognosis and limited therapeutic options. This study investigates the prognostic and therapeutic implications of copper-induced cell death-related long non-coding RNAs (lncRNAs) in LUSC using data from The Cancer Genome Atlas. Five lncRNAs (AC010328.1, LINC01740, AL358613.2, MIR3945HG, AC002467.1) were identified as independent prognostic markers and incorporated into a risk score model to stratify patients into high- and low-risk groups. Survival analyses revealed significant differences in overall survival, with the high-risk group exhibiting higher immune evasion potential and poorer response to immunotherapy. Functional enrichment analyses highlighted the involvement of these lncRNAs in drug metabolism and tumor biology. Furthermore, tumor mutation burden analysis and immune dysfunction evaluation confirmed the clinical relevance of the model, identifying high-risk patients as more sensitive to targeted drugs such as Quizartinib and Dasatinib. A Nomogram integrating lncRNA risk scores and clinical factors demonstrated robust predictive accuracy for 1-, 3-, and 5-year survival outcomes. This study provides novel biomarkers and actionable insights for improving prognostic assessment and personalizing immunotherapy strategies for LUSC patients.