ORIGINAL RESEARCH article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
This article is part of the Research TopicAdvancements in Immune Heterogeneity in Inflammatory Diseases and Cancer: New Targets, Mechanisms, and StrategiesView all 21 articles
Identification of a ubiquitin-binding domain protein, CD2AP, in predicting the prognosis and treatment of lung adenocarcinoma
Provisionally accepted
- 1Ophthalmology Medical Center, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
- 2Department of Cardiothoracic Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
- 3Department of Oncology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
- 4Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
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 tumorigenesis. 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.
Keywords: Lung Adenocarcinoma, ubiquitination-related molecules, CD2-associated protein, drug sensitivity, molecular docking
Received: 16 Oct 2025; Accepted: 20 Nov 2025.
Copyright: © 2025 Dai, Li, Mingfeng, Huang, Bo, Yin and Ye. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Ying Ye, yey1227@hospital.cqmu.edu.cn
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.