Open Access

REVIEW

RNA Expression Signatures in Glioblastoma: A Systematic Review of Tumour Biology and Therapeutic Targets

Amber Hassan¹, Badr Hafiz², Taghreed Alsinani³, Rakan Bokhari⁴, Dahlia Mirdad⁵, Awab Tayyib⁵, Alaa Alkhotani⁶, Ahmad Fallata⁷, Iman Mirza⁸, Eyad Faizo^9,10, Saleh Baeesa², Huda Alghefari¹¹, Maher Kurdi^11,*

1 European School of Molecular Medicine, University of Milan, Milan, 20139, Italy
2 Department of Neurosciences, King Faisal Specialist Hospital and Research Center, Jeddah, 21499, Saudi Arabia
3 Department of Neurosurgery, King Fahad Hospital, Jeddah, 21196, Saudi Arabia
4 Department of Surgery, Faculty of Medicine, King Abdulaziz University, Jeddah, 21589, Saudi Arabia
5 Department of Pathology, Faculty of Medicine, University of Jeddah, Jeddah, 21589, Saudi Arabia
6 Department of Pathology, College of Medicine, Umm Al-Qura University, Makkah, 21955, Saudi Arabia
7 Department of Internal Medicine, Faculty of Medicine, University of Tabuk, Tabuk, 71491, Saudi Arabia
8 Department of Family Medicine, Faculty of Medicine, University of Tabuk, Tabuk, 71491, Saudi Arabia
9 Department of Surgery, Faculty of Medicine, University of Tabuk, Tabuk, 71491, Saudi Arabia
10 Department of Neuroscience, Doctor Suliman Fakeeh Hospital, Jeddah, 21461, Saudi Arabia
11 Department of Pathology, Faculty of Medicine, King Abdulaziz University, Rabigh, 21911, Saudi Arabia

* Corresponding Author: Maher Kurdi. Email:

(This article belongs to the Special Issue: The Identification of Novel Therapeutic Targets and Elucidation of Molecular Mechanisms of Tumorigenesis)

Oncology Research 2025, 33(11), 3293-3325. https://doi.org/10.32604/or.2025.070031

Received 06 July 2025; Accepted 27 August 2025; Issue published 22 October 2025

Abstract

Background: Glioblastoma (GBM) remains the most aggressive primary brain tumour in adults, marked by pronounced cellular heterogeneity, diffuse infiltration, and resistance to conventional treatment. In recent years, transcriptomic profiling has provided valuable insights into the molecular mechanisms that govern the progression of glioblastoma. This systematic review aims to synthesise the current literature on dysregulated gene expression in GBM, focusing on gene signatures associated with stemness, immune modulation, extracellular matrix remodelling, metabolic adaptation, and therapeutic resistance. Methods: We conducted a systematic search of PubMed, The Cancer Genome Atlas (TCGA), Chinese Glioma Genome Atlas (CGGA), and the GlioVis portal for studies published between January 2005 and April 2025, limited to English-language reports. Studies were eligible if they included adult glioblastoma tissue or patient-derived datasets and reported gene-level expression or clinical associations. Reviews, commentaries, and studies on non-GBM gliomas were excluded. Screening followed the PRISMA 2020 checklist, with 410 records initially identified, 90 duplicates removed, and 125 studies retained after full-text review. Data were synthesised descriptively, and findings were validated against TCGA/CGGA expression datasets to ensure consistency across cohorts. Results: We categorised recurrently dysregulated genes by their biological function, including transcription factors (SOX2, ZEB2), growth factor receptors (EGFR, PDGFRA), immune-related markers (PD-L1, TAP1, B2M), extracellular matrix regulators (MMP2, LAMC1, HAS2), and metabolic genes (SLC7A11, PRMT5, NRF2). For each group, we examine the functional consequences of transcriptional alterations and their role in driving key glioblastoma phenotypes, including angiogenesis, immunosuppression, invasiveness, and recurrence. Conclusion: We further discuss the prognostic implications of these gene signatures and evaluate their potential utility in precision medicine, including current clinical trials that target molecular pathways identified through transcriptomic data. This review highlights the power of gene expression profiling to stratify glioblastoma subtypes and improve personalised therapeutic strategies.

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Supplementary Material

Supplementary Material File

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