Work

Identification of a ubiquitin-binding domain protein, CD2AP, in predicting the prognosis and treatment of lung adenocarcinoma

Year: 2025

Type: article

Abstract: Background Lung adenocarcinoma remains a leading cause of cancer mortality, necessitating novel prognostic biomarkers and therapeutic targets. Ubiquitination, a crucial post-translational modification, is deeply implicated in tumourigenesis. This study aims to identify key ubiquitination-related regulators in LUAD and investigate their clinical significance, with a particular focus on CD2AP . Methods We analysed transcriptomic data from TCGA and GEO databases to identify survival-related ubiquitination genes. Proteomic data from the CPTAC database validated key findings. Functional enrichment, immune cell infiltration, and single-cell RNA sequencing (scRNA-seq) analyses were performed to explore the role of CD2AP . Drug sensitivity and molecular docking were used to identify potential therapeutics. Experimental validation included qPCR, Western Blot, immunofluorescence, and functional assays in A549 cells. Results CD2AP was identified as a central regulator, with its mRNA and protein levels significantly elevated in LUAD tissues, and this elevation was associated with poor survival. CD2AP expression correlated with TMB, immune infiltration (particularly monocytes/macrophages), and advanced T stage. scRNA-seq confirmed CD2AP enrichment in monocytes and revealed enhanced communication between CD2AP + tumour cells and monocytes. Two drugs, afatinib and dasatinib, were identified as potential CD2AP -targeting agents via molecular docking. Functional experiments confirmed that silencing CD2AP significantly suppressed the proliferation and migration of A549 cells. Conclusions Our study identifies CD2AP as a key oncoprotein in LUAD. Our findings suggest that targeting CD2AP represents a promising therapeutic strategy for patients with LUAD. Integrating CD2AP assessment into clinical practice may enhance personalised treatment planning and prognostic evaluation for patients with LUAD.

Source: Frontiers in Immunology

DOI: 10.3389/fimmu.2025.1726531