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<p>Differentiating pseudoprogression (PsP) from recurrence in cases of glioblastoma (GBM) after chemoradiotherapy is challenging, with neuroimaging as the only non-invasive method. In this study, we aimed to identify a blood biomarker for precise disease monitoring and investigated the role of Ataxin-2 (ATXN2). Blood samples (n = 45) from patients with suspected recurrence, including eight with PSP, were analyzed. In addition, tumor tissue samples (n = 22), including those from seven patients who also provided blood samples, were examined. Protein levels were assessed using quantitative proteomics and ELISA. ATXN2 levels were measured via western blotting, and localization was determined through immunohistochemistry and immunocytochemistry. ATXN2 knockdown was performed in glioma cell lines to assess its effects on proliferation, migration, and invasion. Proteomics identified ATXN2 as a potential biomarker. ELISA showed significantly higher serum ATXN2 levels in recurrence than in PsP (p = 0.028). ATXN2 ≥ 11.0&#xa0;ng/mL and ≥ 8&#xa0;months post-chemoradiotherapy distinguished recurrence from PsP (AUC = 0.82, sensitivity = 67.6%, specificity = 87.5%). ATXN2 was highly expressed in GBM tissues, localized in neurons and glioma cells, and its knockdown enhanced proliferation, migration, and invasion via ERK phosphorylation. ATXN2, highly expressed in GBM, may serve as a potential blood biomarker for distinguishing PsP from recurrence.</p>

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Ataxin-2 as a candidate blood biomarker for estimating disease status in cases of suspected glioblastoma recurrence

  • 期刊论文

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  • 发表日期：

    2025年9月22日

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  • Farida Garaeva,
  • Riho Nakajima,
  • Sho Tamai,
  • Kensuke Tateishi,
  • Akitake Mukasa,
  • Shinji Kawabata,
  • Hiroaki Nagashima,
  • Manabu Natsumeda,
  • Nozomi Hirai,
  • Shota Tanaka,
  • Shigeo Ohba,
  • Nayuta Higa,
  • Yoshiki Arakawa,
  • Akihide Kondo,
  • Hidehiro Kohzuki,
  • Shinichiro Koizumi,
  • Yutaka Fujioka,
  • Tatsuya Abe,
  • Hemragul Sabit,
  • Masashi Kinoshita,
  • Yasuo Uchida,
  • Sumio Ohtsuki,
  • Mitsutoshi Nakada

摘要

Differentiating pseudoprogression (PsP) from recurrence in cases of glioblastoma (GBM) after chemoradiotherapy is challenging, with neuroimaging as the only non-invasive method. In this study, we aimed to identify a blood biomarker for precise disease monitoring and investigated the role of Ataxin-2 (ATXN2). Blood samples (n = 45) from patients with suspected recurrence, including eight with PSP, were analyzed. In addition, tumor tissue samples (n = 22), including those from seven patients who also provided blood samples, were examined. Protein levels were assessed using quantitative proteomics and ELISA. ATXN2 levels were measured via western blotting, and localization was determined through immunohistochemistry and immunocytochemistry. ATXN2 knockdown was performed in glioma cell lines to assess its effects on proliferation, migration, and invasion. Proteomics identified ATXN2 as a potential biomarker. ELISA showed significantly higher serum ATXN2 levels in recurrence than in PsP (p = 0.028). ATXN2 ≥ 11.0 ng/mL and ≥ 8 months post-chemoradiotherapy distinguished recurrence from PsP (AUC = 0.82, sensitivity = 67.6%, specificity = 87.5%). ATXN2 was highly expressed in GBM tissues, localized in neurons and glioma cells, and its knockdown enhanced proliferation, migration, and invasion via ERK phosphorylation. ATXN2, highly expressed in GBM, may serve as a potential blood biomarker for distinguishing PsP from recurrence.