Abstract
BACKGROUND: Lung Adenocarcinoma (LUAD) is a major subtype of Non-Small Cell Lung Cancer (NSCLC) with poor prognosis. Despite advances in molecular targeted therapy and immunotherapy, the five-year survival rate remains low. Disulfidptosis, a novel cell death mechanism, may play a role in tumor progression. CD2AP (CD2-associated protein), a key gene related to Disulfidptosis, is involved in cytoskeleton reorganization and signaling. This study aimed to explore CD2AP's function in LUAD and its potential as a biomarker and therapeutic target through multi-omics analysis. METHODS: We analyzed CD2AP expression and clinical significance in LUAD using data from TCGA, GEO, and other public databases. We employed transcriptomics, methylation analysis, immune infiltration assays, and spatial transcriptomics. Kaplan-Meier survival analysis was used to assess the relationship between CD2AP expression and prognosis. Enrichment analysis identified biological processes and pathways related to CD2AP, while its association with the immune microenvironment and drug sensitivity was also evaluated. RESULTS: CD2AP was significantly overexpressed in LUAD, and high expression correlated with poorer prognosis, including overall survival and progression-free survival. Enrichment analysis showed CD2AP is involved in cell adhesion, PI3K-Akt signaling, and immune escape, suggesting it promotes LUAD progression through these pathways. High CD2AP expression was associated with alterations in the tumor immune microenvironment and drug sensitivity, particularly to chemotherapeutics like Cisplatin, Etoposide, and Paclitaxel, and resistance to targeted therapies like Gefitinib. Spatial transcriptomics revealed higher CD2AP expression in tumor regions, especially in malignant cell-enriched areas. CONCLUSION: This study highlights CD2AP's critical role in LUAD, particularly in immune microenvironment modulation, metabolic reprogramming, and drug response. CD2AP's high expression is linked to poor prognosis and may serve as a potential target for immunotherapy and drug response prediction.