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Background <p>Glioblastoma multiforme (GBM) is the most aggressive brain tumor, with poor overall survival (OS). <i>TP53</i>, a key tumor suppressor gene, is frequently altered in GBM, but the prognostic relevance of its promoter methylation has not been investigated in the Pakistani population.</p> Methods <p>In this retrospective study, <i>TP53</i> promoter methylation was assessed in 48 primary GBM patients and 60 healthy controls using methylation-sensitive high-resolution melting analysis. Associations with clinicopathological features and treatment modalities were assessed using Fisher’s exact/Chi-square test. OS was estimated with Kaplan-Meier survival analysis and Cox proportional hazard regression was performed as exploratory analysis.</p> Results <p><i>TP53</i> promoter methylation was detected in 72.9% (35/48) of GBM patients but in none of the controls. <i>TP53</i> methylation showed no significant difference across clinicopathological variables or improved OS. However, patients with unmethylated <i>TP53</i> who received post-surgical chemoradiotherapy had significantly longer OS (65.6 months; 95% CI: 60.6–70.5; <i>P</i> = 0.040) compared with methylated cases (19.2 months; 95% CI: 9.9–28.4). The effect was more pronounced in patients with concurrent <i>MGMT</i> methylation (unmethylated <i>TP53</i>: 65.6 months; 95% CI: 60.6–70.5 vs. methylated <i>TP53</i>: 13.2 months; 95% CI: 9.2–17.2; <i>P</i> = 0.018).</p> Conclusion <p>This is the first study to report frequent <i>TP53</i> promoter methylation in Pakistani GBM patients. Our exploratory findings suggest that combined <i>MGMT</i> methylation and <i>TP53</i> unmethylation may confer a survival advantage. Larger prospective studies are needed to validate these findings before clinical application.</p>

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High frequency and prognostic significance of TP53 promoter methylation in Pakistani glioblastoma patients

  • 期刊论文

  • 发表日期：

    2025年11月24日

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  • Ahad Naveed,
  • Noor Muhammad,
  • Afshan Khanum,
  • Asif Loya,
  • Muhammad Usman Rashid

摘要

Background

Glioblastoma multiforme (GBM) is the most aggressive brain tumor, with poor overall survival (OS). TP53, a key tumor suppressor gene, is frequently altered in GBM, but the prognostic relevance of its promoter methylation has not been investigated in the Pakistani population.

Methods

In this retrospective study, TP53 promoter methylation was assessed in 48 primary GBM patients and 60 healthy controls using methylation-sensitive high-resolution melting analysis. Associations with clinicopathological features and treatment modalities were assessed using Fisher’s exact/Chi-square test. OS was estimated with Kaplan-Meier survival analysis and Cox proportional hazard regression was performed as exploratory analysis.

Results

TP53 promoter methylation was detected in 72.9% (35/48) of GBM patients but in none of the controls. TP53 methylation showed no significant difference across clinicopathological variables or improved OS. However, patients with unmethylated TP53 who received post-surgical chemoradiotherapy had significantly longer OS (65.6 months; 95% CI: 60.6–70.5; P = 0.040) compared with methylated cases (19.2 months; 95% CI: 9.9–28.4). The effect was more pronounced in patients with concurrent MGMT methylation (unmethylated TP53: 65.6 months; 95% CI: 60.6–70.5 vs. methylated TP53: 13.2 months; 95% CI: 9.2–17.2; P = 0.018).

Conclusion

This is the first study to report frequent TP53 promoter methylation in Pakistani GBM patients. Our exploratory findings suggest that combined MGMT methylation and TP53 unmethylation may confer a survival advantage. Larger prospective studies are needed to validate these findings before clinical application.