TY - JOUR
T1 - Ataxin-2 as a candidate blood biomarker for estimating disease status in cases of suspected glioblastoma recurrence
AU - Garaeva, Farida
AU - Nakajima, Riho
AU - Tamai, Sho
AU - Tateishi, Kensuke
AU - Mukasa, Akitake
AU - Kawabata, Shinji
AU - Nagashima, Hiroaki
AU - Natsumeda, Manabu
AU - Hirai, Nozomi
AU - Tanaka, Shota
AU - Ohba, Shigeo
AU - Higa, Nayuta
AU - Arakawa, Yoshiki
AU - Kondo, Akihide
AU - Kohzuki, Hidehiro
AU - Koizumi, Shinichiro
AU - Fujioka, Yutaka
AU - Abe, Tatsuya
AU - Sabit, Hemragul
AU - Kinoshita, Masashi
AU - Uchida, Yasuo
AU - Ohtsuki, Sumio
AU - Nakada, Mitsutoshi
N1 - Publisher Copyright:
© The Author(s) 2025.
PY - 2026/4
Y1 - 2026/4
N2 - 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.
AB - 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.
KW - Ataxin-2
KW - Biomarker
KW - Glioblastoma
KW - Pseudoprogression
KW - Recurrence
UR - https://www.scopus.com/pages/publications/105016886688
UR - https://www.scopus.com/pages/publications/105016886688#tab=citedBy
U2 - 10.1007/s10014-025-00517-z
DO - 10.1007/s10014-025-00517-z
M3 - Article
C2 - 40982134
AN - SCOPUS:105016886688
SN - 1433-7398
VL - 43
SP - 43
EP - 55
JO - Brain Tumor Pathology
JF - Brain Tumor Pathology
IS - 2
ER -
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