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Background <p>Cells expressing stemness markers have the potential to convert normal stem cells or cancer cells into cancer stem cells (CSCs), and their overexpression is known to foster tumor progression. They form a dynamic aspect of the tumor micro-environment and are involved in tumor relapse/recurrence and resistance to treatment. The expression of several stemness markers is linked with survival &amp; prognosis of glioma patients. Still, no single marker is recognized to have substantial diagnostic value and the best predictive power for survival and prognosis. Therefore, we undertook an evaluation of the systemic expression of a panel of HMGA1, hTERT, CD117, and PDGFRα as predictors of recurrence in glioma.</p> Methods <p>The circulating levels of the aforementioned stemness markers were estimated in serum/plasma from <i>n</i> = 15 glioma patients using enzyme-linked immunosorbent assay (ELISA) to establish their values at the time of diagnosis and recurrence. Their expression was corroborated and validated in corresponding glioma tissues by fluorescence-immunohistochemical staining. Kaplan-Meier curves were generated to assess the influence of these markers on overall survival and relapse-free survival. Univariate Cox regression hazards ratio was employed to assess risk factors of adverse outcomes. HMGA1 and hTERT were targeted in vitro in the glioblastoma modelusing 10 µM curcumin to curtail stemness and migration potential.</p> Results <p>Soluble HMGA1, hTERT, CD117, and PDGFRα were found to be significantly elevated in the pre-treatment glioma group compared to controls (<i>p</i> = 0.034, <i>p</i> = 0.0002, <i>p</i> = 0.0003, and <i>p</i> = 0.024, respectively). The results of tissue expression of the biomarkers were consistent with systemic levels. Paired sample analysis at diagnosis and relapse revealed significantly upregulated systemic hTERT and PDGFRα levels at relapse (<i>p</i> = 0.047 and <i>p</i> = 0.013, respectively). Log-rank analysis and univariate Cox regression hazards ratio presented a higher expression of hTERT and HMGA1 to be significantly correlated with a shorter OS and RFS. Cells targeted with 10 µM curcumin displayed a reduction in hTERT and HMGA1 protein expression at 24&#xa0;h, along with a decrease in migration potential. The systemic levels of these markers have shown promise as prognostic indicators of recurrence.</p>

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Biomarkers of the tumor microenvironment for prognostication of recurrence in glioma and targeting stemness using an adjuvant

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月18日

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  • Puneet Gandhi,
  • Kavita Peter,
  • Sandeep Sorte,
  • Nitin Garg

摘要

Background

Cells expressing stemness markers have the potential to convert normal stem cells or cancer cells into cancer stem cells (CSCs), and their overexpression is known to foster tumor progression. They form a dynamic aspect of the tumor micro-environment and are involved in tumor relapse/recurrence and resistance to treatment. The expression of several stemness markers is linked with survival & prognosis of glioma patients. Still, no single marker is recognized to have substantial diagnostic value and the best predictive power for survival and prognosis. Therefore, we undertook an evaluation of the systemic expression of a panel of HMGA1, hTERT, CD117, and PDGFRα as predictors of recurrence in glioma.

Methods

The circulating levels of the aforementioned stemness markers were estimated in serum/plasma from n = 15 glioma patients using enzyme-linked immunosorbent assay (ELISA) to establish their values at the time of diagnosis and recurrence. Their expression was corroborated and validated in corresponding glioma tissues by fluorescence-immunohistochemical staining. Kaplan-Meier curves were generated to assess the influence of these markers on overall survival and relapse-free survival. Univariate Cox regression hazards ratio was employed to assess risk factors of adverse outcomes. HMGA1 and hTERT were targeted in vitro in the glioblastoma modelusing 10 µM curcumin to curtail stemness and migration potential.

Results

Soluble HMGA1, hTERT, CD117, and PDGFRα were found to be significantly elevated in the pre-treatment glioma group compared to controls (p = 0.034, p = 0.0002, p = 0.0003, and p = 0.024, respectively). The results of tissue expression of the biomarkers were consistent with systemic levels. Paired sample analysis at diagnosis and relapse revealed significantly upregulated systemic hTERT and PDGFRα levels at relapse (p = 0.047 and p = 0.013, respectively). Log-rank analysis and univariate Cox regression hazards ratio presented a higher expression of hTERT and HMGA1 to be significantly correlated with a shorter OS and RFS. Cells targeted with 10 µM curcumin displayed a reduction in hTERT and HMGA1 protein expression at 24 h, along with a decrease in migration potential. The systemic levels of these markers have shown promise as prognostic indicators of recurrence.