Abstract
Objective. The extracellular matrix (ECM) plays a key role in glioblastoma (GB) progression by shaping an immunosuppressive tumor microenvironment and acting as a drug penetration barrier. This study performed an integrative analysis of seven publicly available GB transcriptomic datasets using two analytical approaches to identify key ECM core genes driving tumor remodeling and patient survival.
Results. Three gene signatures were identified, reflecting core ECM remodeling processes in GB. Signature №1 (17 genes), Signature №2 (14 genes), and minimal Signature №3 (COL4A1, COL4A2, AEBP1, TNC) are prospective gene panels for targeted therapy and patient stratification. Elevated expression of all three signatures markedly diminishes survival in GB patients (Kaplan – Meier log-rank test, p < 0,05). In the training cohorts, Signature №2 demonstrated the strongest prognostic performance according to univariable and multivariable Cox regression analyses (HR = 1.67, p = 0.006; HR = 1.46, p = 0.051, respectively). Independent validation in the CGGA693 and CGGA325 cohorts showed that the minimal Signature №3 had the greatest reproducibility, retaining a statistically significant association with overall survival in multivariable models in both cohorts (p = 0.01).
Conclusion. The identified ECM gene signatures show potential as biomarkers for risk stratification and targeted therapy in GB. Thus, Signature №2 exhibited the highest prognostic value in the training cohort, whereas minimal Signature №3 yielded the most robust results during independent validation. These findings require further experimental validation and assessment of the clinical applicability of the identified genes as diagnostic biomarkers and potential therapeutic targets.
Authors and affiliations
https://elibrary.ru/nnpfai D.O. Kuzmina, A.E. Yuzhalin
Sirius University of Science and Technology, Olympic Avenue, 1, Sirius, 354340, Russian Federation
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