Gene expression profiling: a top list of blood-based genes between low- and high-grade gliomas in Malaysian brain tumour patients

Muhamad Farid Zulkifle^1,2*, Shalini Ponnusamy^1,6, Nursaedah Abdullah Aziz¹, Sok Fang Khor^1,7, Roslina Husaini^1,3, Fauziah Kassim⁴, Zubaidah Zakaria¹, Stephen Navendran Ponnampalam^1,5

1. Cancer Research Centre (CaRC), Institute for Medical Research (IMR), National Institutes of Health (NIH), Ministry of Health (MOH), Setia Alam, 40170 Shah Alam, Selangor Darul Ehsan, Malaysia

2. Department of Pathology, Faculty of Medicine, Universiti Kebangsaan Malaysia Medical Centre (UKMMC), 56000 Cheras, Wilayah Persekutuan Kuala Lumpur, Malaysia

3. Centre for Coordination Clinical Research Networking (CCRN), Institute for Clinical Research (ICR), National Institutes of Health (NIH), Ministry of Health (MOH), Setia Alam, 40170 Shah Alam, Selangor Darul Ehsan, Malaysia

4. Department of Pathology, Hospital Kuala Lumpur (HKL), Ministry of Health (MOH), Jalan Pahang, 50586 Kuala Lumpur, Wilayah Persekutuan Kuala Lumpur, Malaysia

5. Department of Genetics, Hospital Tunku Azizah (HTA), Ministry of Health (MOH), 50300 Kuala Lumpur, Wilayah Persekutuan Kuala Lumpur, Malaysia

6. Department of Pathology, Hospital Raja Permaisuri Bainun (HRPB), Ministry of Health (MOH), 30450 Ipoh, Perak Darul Ridzuan, Malaysia

7. Environmental Health Research Centre (EHRC), Institute for Medical Research (IMR), National Institutes of Health (NIH), Ministry of Health (MOH), Setia Alam, 40170 Shah Alam, Selangor Darul Ehsan, Malaysia

*Corresponding author: Muhamad Farid Zulkifle. This email address is being protected from spambots. You need JavaScript enabled to view it.

CITATION: Zulkifle, M. F., Ponnusamy, S., Abdullah Aziz, N., Khor, S. F., Husaini, R., Kassim, F., Zakaria, Z., & Ponnampalam, S. N. (2025). Gene expression profiling: a top list of blood-based genes between low- and high-grade gliomas in Malaysian brain tumour patients. International Medical Research Journal, 11(2), 40170. https://doi.org/https://doi.org/10.63719/imrj.2025.11.02.009

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ABSTRACT

Gliomas are the most common primary brain tumours, classified into low- and high-grade types with markedly different prognoses and treatment strategies. This study aimed to identify whole-blood transcriptomic signatures capable of distinguishing between glioma grades to support minimally invasive diagnostics. Whole-blood RNA profiling was performed in 17 patients with low-grade (n=8) and high-grade (n=9) gliomas using the Agilent 4×44K whole human genome microarray. Differential expression analysis, guided by the sentinel principle, revealed distinct clustering confirmed by principal component analysis. After Benjamini–Hochberg correction, 3,806 of 44,000 genes were significantly differentially expressed (corrected p <0.01, ≥2-fold change), including 2,589 downregulated and 1,217 upregulated genes in low- and high-grade gliomas. Key deregulated genes included SKI, BAX, BCL2, DLK1, AXIN2, BMI1, and AKT3, many of which are known tumour suppressors or oncogenes with established roles in gliomagenesis. Quantitative polymerase chain reaction (qPCR) validation was conducted for one selected gene, confirming the microarray result. Whole-blood transcriptomic profiling can differentiate glioma grades and identifies candidate biomarkers with potential diagnostic and therapeutic value. However, the small cohort size and limited validation highlight the need for larger, multicentre studies with expanded confirmatory assays before clinical translation.

KEYWORDS: Blood-based, Gene expression, Biomarkers, Brain tumour, Gliomas.