Ataxin-2 as a candidate blood biomarker for estimating disease status in cases of suspected glioblastoma recurrence
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.
Authors
- Nayuta Higa (ORCID: https://orcid.org/0000-0001-8853-8769)
- Farida Garaeva
- Shinji Kawabata (ORCID: https://orcid.org/0000-0001-5007-5279)
- Hiroaki Nagashima (ORCID: https://orcid.org/0000-0003-0685-7382)
- Akitake Mukasa (ORCID: https://orcid.org/0000-0001-7776-9086)
- Shinichiro Koizumi (ORCID: https://orcid.org/0000-0003-1104-6824)
- Masashi Kinoshita (ORCID: https://orcid.org/0000-0002-2148-8231)
- Shigeo Ohba (ORCID: https://orcid.org/0000-0003-4575-0238)
- Manabu Natsumeda (ORCID: https://orcid.org/0000-0003-3098-8323)
- Mitsutoshi Nakada (ORCID: https://orcid.org/0000-0001-9419-6101)
- Hidehiro Kohzuki
- Sumio Ohtsuki (ORCID: https://orcid.org/0000-0003-4634-7133)
- Hemragul Sabit
- Yoshiki Arakawa (ORCID: https://orcid.org/0000-0003-4626-4645)
- Sho Tamai (ORCID: https://orcid.org/0000-0002-5403-7111)
- Akihide Kondo (ORCID: https://orcid.org/0000-0003-1729-4490)
- Yutaka Fujioka (ORCID: https://orcid.org/0000-0002-8506-9343)
- Kensuke Tateishi
- Yasuo Uchida (ORCID: https://orcid.org/0000-0001-9860-1979)
- Tatsuya Abe (ORCID: https://orcid.org/0000-0002-7215-3597)
- Riho Nakajima
- Nozomi Hirai
- Shota Tanaka (ORCID: https://orcid.org/0000-0002-3053-6928)
Institutions
- Kanazawa University (JP)
- Kagoshima University (JP)
- Hiroshima University (JP)
- Toho University (JP)
- Kyushu University (JP)
- Fujita Health University (JP)
- Okayama University (JP)
- Saga University (JP)
- Kazan Federal University (RU)
- Kyoto University (JP)
- Hamamatsu University School of Medicine (JP)
- Juntendo University (JP)
- Toho University Ohashi Medical Center (JP)
- University of Tsukuba Hospital (JP)
- Kobe University (JP)
- Niigata University (JP)
- The University of Tokyo (JP)
- Yokohama City University (JP)
- Osaka University of Pharmaceutical Sciences (JP)
- Kumamoto University (JP)
Publication Details
- Journal
- Brain Tumor Pathology
- Published
- 2025-09-22
- DOI
- https://doi.org/10.1007/s10014-025-00517-z
- Primary Topic
- Glioma Diagnosis and Treatment
- Type
- article
- Field-Weighted Citation Impact
- 0.00