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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1540578
This article is part of the Research Topic Harnessing Molecular Insights for Enhanced Drug Sensitivity and Immunotherapy in Cancer View all 17 articles

Development and Functional Validation of a Disulfidoptosis-Related Gene Prognostic Model for Lung Adenocarcinoma Based on Bioinformatics and Experimental Validation

Provisionally accepted
Tao Shen Tao Shen 1Zhuming Lu Zhuming Lu 2Sisi Yang Sisi Yang 3Dongxi Zhang Dongxi Zhang 2Yongwen Ke Yongwen Ke 2Zhuowen Chen Zhuowen Chen 2Jinqiang Wu Jinqiang Wu 4Weidong Wu Weidong Wu 5*
  • 1 Department of Surgery, First Clinical Medical College of Jinan University, Guangzhou, China
  • 2 Department of Thoracic Surgery, Jiangmen Central Hospital, Jiangmen, China
  • 3 Department of Psychology, Jiangmen Third People's Hospital, Jiangmen, China
  • 4 Department of Cardiothoracic Vascular Surgery, The Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, China
  • 5 Department of Cardiothoracic Vascular Surgery, Guangzhou Red Cross Hospital of Jinan University, Guangzhou, China

The final, formatted version of the article will be published soon.

    BackgroundDisulfidoptosis is increasingly linked to cancer progression, yet its immunological impacts and prognostic value in lung adenocarcinoma (LUAD) remain poorly understood. This study aims to delineate the predictive significance of disulfidoptosis-related genes (DRGs) in LUAD, their potential as therapeutic targets, and their interaction with the tumor microenvironment.MethodsWe analyzed the expression profiles of 23 DRGs and survival data, performing consensus clustering to identify molecular subtypes. Survival analysis and gene set variation analysis (GSVA) were used to explore cluster differences. Key DRGs were selected for Cox and LASSO regression to develop a prognostic model. Tensin4 (TNS4), a key gene in the model, was further evaluated through immunohistochemistry (IHC) in LUAD and normal tissues and gene knockdown experiments in vitro. ResultsTwo clusters were identified, with 225 differentially expressed genes. A six-gene signature was developed, which classified LUAD patients into high- and low-risk groups, showing significant survival differences. The risk score independently predicted LUAD prognosis and correlated with immunotherapy responses. IHC showed elevated TNS4 levels in LUAD tissues, while in vitro TNS4 knockdown reduced both cell proliferation and migration.ConclusionThis study highlights the role of DRGs in LUAD, with a validated gene signature offering new avenues for targeted therapies, potentially improving LUAD treatment outcomes.

    Keywords: LUAD, disulfidptosis, Tumor microenvironments, prognosis, Immunotherapy

    Received: 06 Dec 2024; Accepted: 22 Jan 2025.

    Copyright: © 2025 Shen, Lu, Yang, Zhang, Ke, Chen, Wu and Wu. 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: Weidong Wu, Department of Cardiothoracic Vascular Surgery, Guangzhou Red Cross Hospital of Jinan University, Guangzhou, China

    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.