ORIGINAL RESEARCH article

Front. Oncol.

Sec. Cancer Molecular Targets and Therapeutics

Volume 15 - 2025 | doi: 10.3389/fonc.2025.1531937

This article is part of the Research TopicNovel Molecular Targets in Cancer TherapyView all 36 articles

High expression of SOX9 is a diagnostic and prognostic indicator of glioma

Provisionally accepted
Libo  XuLibo Xu1Zhenhao  WangZhenhao Wang1Mao  LiMao Li2Qingsong  LiQingsong Li1*
  • 1The Second Affiliated Hospital of Harbin Medical University, Harbin Medical University, Harbin, Heilongjiang, China
  • 2Davis, University of California, Los Angeles, California, United States

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

Background: Glioblastoma (GBM) originates from neuroepithelial tissue and is one of the most common intracranial malignant tumors in adults, with high recurrence rate and poor prognosis. In recent years, SOX9 has been reported to play an important role in many diseases and cancers, and is a promising target, but it has been rarely reported in GBM.Methods: RNA sequencing data of GBM were obtained from the Cancer Genome Atlas (TCGA) database and the Genotype-Tissue Expression (GTEx) database for analysis of SOX9 expression and differentially expressed genes (DEGs). Moreover, functional enrichment analysis of GBM-related DEGs was performed by GO/KEGG, GSEA, and protein-protein interaction (PPI) network. Additionally, the clinical significance of SOX9 in GBM was assessed by Kaplan-Meier Cox regression and prognostic model. What's more, we analyzed SOX9-related immune cell infiltration and expression of immune checkpoints in GBM. The incorporated studies were analyzed using the R package.Results: SOX9 was highly expressed in a range of malignant tumor tissues, including GBM. Surprisingly, high SOX9 expression was remarkably associated with better prognosis in the lymphoid invasion subgroups in a sample of 478 cases (P < 0.05).Totally, 126 differentially significant genes (DSGs) were identified between high-and low-expression group, of which 29 genes were upregulated and 97 genes were downregulated. Furthermore, high expression of SOX9 was an independent prognostic factor for IDH (isocitrate dehydrogenase)-mutant in Cox regression analysis. Screening was performed by LASSO coefficients to select non-zero variables that satisfied the coefficients of lambda. min, and four genes were screened out. OR4K2 and IDH status were prognostic factors associated with THCA in multifactorial COX regression analysis. SOX9, OR4K2 and IDH status were included in the nomogram prognostic model. Correlation analysis indicated SOX9 expression was correlated with immune cell infiltration and expression of immune checkpoints in GBM.

Keywords: GBM, SOX9, Immune Cell Infiltration, prognostic mode, targeted therapies

Received: 21 Nov 2024; Accepted: 09 Jun 2025.

Copyright: © 2025 Xu, Wang, Li and Li. 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: Qingsong Li, The Second Affiliated Hospital of Harbin Medical University, Harbin Medical University, Harbin, 130012, Heilongjiang, 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.