Skip to main content

ORIGINAL RESEARCH article

Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1462064
This article is part of the Research Topic New Insights into Immune Regulation for Two Sides of the Same Coin: Cancer and Autoimmunity View all 3 articles

Integrated multi-level omics profiling of disulfidptosis identifis SPAG4 as an innovative immunotherapeutic target in glioblastoma

Provisionally accepted
Shenbo Chen Shenbo Chen Man Zeng Man Zeng Taixue Chen Taixue Chen Hui Ding Hui Ding Jiahan Lin Jiahan Lin Fuyue Ye Fuyue Ye Ran Wu Ran Wu LiangWang Yang LiangWang Yang Kun Yang Kun Yang *
  • First Affiliated Hospital of Hainan Medical University, Haikou, Hainan Province, China

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

    Objective: To investigate the association between disulfidptosis-related genes (DFRGs) and patient prognosis, while concurrently identifying potential therapeutic targets in glioblastoma (GBM). Methods: We retrieved RNA sequencing data and clinical characteristics of GBM patients from the TCGA database. We found there was a total of 6 distinct clusters in GBM, which was identified by the t-SNE and UMAP dimension reduction analysis. Prognostically significant genes in GBM were identified using the limma package, coupled with univariate Cox regression analysis. Machine learning algorithms were then applied to identify central genes. The CIBERSORT algorithm was utilized to assess the immunological landscape across different GBM subtypes. In vitro and in vivo experiments were conducted to investigate the role of SPAG4 in regulating the proliferation, invasion of GBM, and its effects within the immune microenvironment. Results: 23 genes, termed DFRGs, were successfully identified, demonstrating substantial potential for establishing a prognostic model for GBM. Single cell analysis revealed a significant correlation between DFRGs and the progression of GBM. Utilizing individual risk scores derived from this model enabled the stratification of patients into two distinct risk groups, revealing significant variations in immune infiltration patterns and responses to immunotherapy. Utilizing the random survival forests algorithm, SPAG4 was identified as the gene with the highest prognostic significance within our model. In vitro studies have elucidated SPAG4's significant role in GBM pathogenesis, potentially through the regulation of fatty acid metabolism pathways. Our in vivo investigations using a subcutaneous xenograft model have confirmed SPAG4's influence on tumor growth and its capacity to modulate the immune microenvironment. Advanced research hints that SPAG4 might achieve immune evasion by increasing CD47 expression, consequently reducing phagocytosis. Conclusions: These findings highlight SPAG4 as a potential GBM therapeutic target and emphasize the complexity of the immune microenvironment in GBM progression.

    Keywords: Glioblastoma, disulfidptosis, Tumor immune microenvironment, Prognostic model, SPAG4

    Received: 09 Jul 2024; Accepted: 07 Oct 2024.

    Copyright: © 2024 Chen, Zeng, Chen, Ding, Lin, Ye, Wu, Yang and Yang. 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: Kun Yang, First Affiliated Hospital of Hainan Medical University, Haikou, 570102, Hainan Province, 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.