Phosphorylated Hsp27 is mutually exclusive with ATRX loss and the IDH1^R132Hmutation and may predict better prognosis among glioblastomas without the IDH1 mutation and ATRX loss

Abstract

<jats:sec><jats:title>Aim</jats:title><jats:p>To identify biomarkers for accurate classification of glioma.</jats:p></jats:sec><jats:sec><jats:title>Patients and methods</jats:title><jats:p>We evaluated the heat shock protein 27 (Hsp27), phosphorylated Hsp27 (p-Hsp27), ATRX and IDH1<jats:sup>R132H</jats:sup>proteins using immunohistochemistry in 421 glioma tissues. The χ<jats:sup>2</jats:sup> test was used to assess the relationship between molecular alterations and clinico-pathological parameters. Kaplan-Meier survival curves were constructed, and differences were detected by the log-rank test.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>We found that Hsp27 and p-Hsp27 were mainly expressed in aggressive astrocytic gliomas. However, neither Hsp27 nor p-Hsp27 expression was related to survival time for any grade of glioma. Interestingly, p-Hsp27 was mutually exclusive with ATRX loss (ATRX<jats:sup>−</jats:sup>) and the IDH1<jats:sup>R132H</jats:sup> mutation, except for one case of anaplastic astrocytoma. We classified glioblastomas (GBMs) into three subtypes: ATRX<jats:sup>−</jats:sup>/IDH1<jats:sup>R132H</jats:sup>, high p-Hsp27 expression (p-Hsp27<jats:sup>+</jats:sup>) and none of these three markers. ATRX<jats:sup>-</jats:sup>/IDH1<jats:sup>R132H</jats:sup>showed the longest median survival (19.6 months). The prognostic difference between p-Hsp27<jats:sup>+</jats:sup> and none of these three markers was significant (15.0 vs 13.1 months, P=0.045). Moreover, p-Hsp27<jats:sup>+</jats:sup> predicted better sensitivity for standard therapy among GBMs without the IDH1 mutation and ATRX loss (26.3 vs 15.5 months, P=0.008).</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>p-Hsp27 is a novel biomarker of glioma and might have important clinical value for further classification of patients with wild-type IDH1 and normal ATRX expression, for evaluating prognosis and for guidance for adjuvant therapy.</jats:p></jats:sec>

High S phase kinase‑associated protein 2 expression is a potential prognostic biomarker for glioma

“…A previous study reported the clinical relevance of IDH1 mutation in gliomas (28). In the present study, it was observed that patients with IDH1 mutation showed favorable prognosis (P= 0.048; Fig.…”

Overexpression of IGFBP2 mRNA predicts poor survival in patients with glioblastoma

“…For the same cases, we previously reported high expression of Hsp27 protein and isocitrate dehydrogenase 1 (IDH1) mutation in tumors [22]. In the present study, we further investigated TERTp mutation, and simultaneously analyzed the relationship between IGFBP2 mRNA expression and the alterations of TERTp, Hsp27 and IDH1 (Figure 2).…”

“…The following antibodies were used: anti-heat shock protein 27 (Hsp27) antibody (1:500, 50353, CST), anti-IDH1 R132H antibody (working solution, ZM0447, ZSGB-BIO). The immuno-scores for these antibodies were evaluated as previously described [22].…”

FKBP10 promotes proliferation of glioma cells via activating AKT-CREB-PCNA axis

“…TMAs and paraffin-embedded subcutaneous xenograft were cut into 5-μm sections. Immunohistochemistry and evaluation of immunostaining were performed as described previously [ 22 ]. The following primary antibodies were used: anti-FKBP10 antibody (1:2000, 50353, Sigma), anti-Hsp47 antibody (1:1200, sc5293, Santa Cruz), anti- p-CREB (1:1000, 9198S, CST) and PCNA (1:5000, 13110S, CST).…”