PIK3R1Met326Ile germline mutation correlates with cysteine-rich protein 61 expression and poor prognosis in glioblastoma

Abstract Despite therapeutic advances, glioblastoma represents a lethal brain tumor. Recently, research to identify prognostic markers for glioblastoma has intensified. Our previous study demonstrated that median progression-free survival (PFS) and overall survival (OS) of patients with high cystein...

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Autores principales: Yoshihiro Otani, Joji Ishida, Kazuhiko Kurozumi, Tetsuo Oka, Toshihiko Shimizu, Yusuke Tomita, Yasuhiko Hattori, Atsuhito Uneda, Yuji Matsumoto, Hiroyuki Michiue, Shuta Tomida, Takehiro Matsubara, Tomotsugu Ichikawa, Isao Date
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Publicado: Nature Portfolio 2017
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spelling oai:doaj.org-article:3e7ede37e22043e69e63784956e3a78e2021-12-02T11:52:29ZPIK3R1Met326Ile germline mutation correlates with cysteine-rich protein 61 expression and poor prognosis in glioblastoma10.1038/s41598-017-07745-02045-2322https://doaj.org/article/3e7ede37e22043e69e63784956e3a78e2017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-07745-0https://doaj.org/toc/2045-2322Abstract Despite therapeutic advances, glioblastoma represents a lethal brain tumor. Recently, research to identify prognostic markers for glioblastoma has intensified. Our previous study demonstrated that median progression-free survival (PFS) and overall survival (OS) of patients with high cysteine-rich protein 61 (CCN1) expression was significantly shorter than that of patients with low CCN1 expression. To understand the molecular mechanisms that regulate CCN1 expression, we examined 147 tumour samples from 80 patients with glioblastoma and 67 patients with lower grade glioma. Next-generation and Sanger sequencing showed that PIK3R1Met326Ile was more frequent in the CCN1 high expression group (10/37 cases, 27.0%) than the CCN1 low expression group (3/38 cases, 7.9%) in glioblastoma. This mutation was also detected in corresponding blood samples. In multivariate analysis, high CCN1 expression and PIK3R1Met326Ile in glioblastoma patients were prognostic factors for OS [HR = 2.488 (1.298–4.769), p = 0.006] and [HR = 2.089 (1.020–4.277), p = 0.0439], respectively. Thus, the PIK3R1Met326Ile germline appears to be correlated with CCN1 expression and poor prognosis in glioblastoma.Yoshihiro OtaniJoji IshidaKazuhiko KurozumiTetsuo OkaToshihiko ShimizuYusuke TomitaYasuhiko HattoriAtsuhito UnedaYuji MatsumotoHiroyuki MichiueShuta TomidaTakehiro MatsubaraTomotsugu IchikawaIsao DateNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Yoshihiro Otani
Joji Ishida
Kazuhiko Kurozumi
Tetsuo Oka
Toshihiko Shimizu
Yusuke Tomita
Yasuhiko Hattori
Atsuhito Uneda
Yuji Matsumoto
Hiroyuki Michiue
Shuta Tomida
Takehiro Matsubara
Tomotsugu Ichikawa
Isao Date
PIK3R1Met326Ile germline mutation correlates with cysteine-rich protein 61 expression and poor prognosis in glioblastoma
description Abstract Despite therapeutic advances, glioblastoma represents a lethal brain tumor. Recently, research to identify prognostic markers for glioblastoma has intensified. Our previous study demonstrated that median progression-free survival (PFS) and overall survival (OS) of patients with high cysteine-rich protein 61 (CCN1) expression was significantly shorter than that of patients with low CCN1 expression. To understand the molecular mechanisms that regulate CCN1 expression, we examined 147 tumour samples from 80 patients with glioblastoma and 67 patients with lower grade glioma. Next-generation and Sanger sequencing showed that PIK3R1Met326Ile was more frequent in the CCN1 high expression group (10/37 cases, 27.0%) than the CCN1 low expression group (3/38 cases, 7.9%) in glioblastoma. This mutation was also detected in corresponding blood samples. In multivariate analysis, high CCN1 expression and PIK3R1Met326Ile in glioblastoma patients were prognostic factors for OS [HR = 2.488 (1.298–4.769), p = 0.006] and [HR = 2.089 (1.020–4.277), p = 0.0439], respectively. Thus, the PIK3R1Met326Ile germline appears to be correlated with CCN1 expression and poor prognosis in glioblastoma.
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author Yoshihiro Otani
Joji Ishida
Kazuhiko Kurozumi
Tetsuo Oka
Toshihiko Shimizu
Yusuke Tomita
Yasuhiko Hattori
Atsuhito Uneda
Yuji Matsumoto
Hiroyuki Michiue
Shuta Tomida
Takehiro Matsubara
Tomotsugu Ichikawa
Isao Date
author_facet Yoshihiro Otani
Joji Ishida
Kazuhiko Kurozumi
Tetsuo Oka
Toshihiko Shimizu
Yusuke Tomita
Yasuhiko Hattori
Atsuhito Uneda
Yuji Matsumoto
Hiroyuki Michiue
Shuta Tomida
Takehiro Matsubara
Tomotsugu Ichikawa
Isao Date
author_sort Yoshihiro Otani
title PIK3R1Met326Ile germline mutation correlates with cysteine-rich protein 61 expression and poor prognosis in glioblastoma
title_short PIK3R1Met326Ile germline mutation correlates with cysteine-rich protein 61 expression and poor prognosis in glioblastoma
title_full PIK3R1Met326Ile germline mutation correlates with cysteine-rich protein 61 expression and poor prognosis in glioblastoma
title_fullStr PIK3R1Met326Ile germline mutation correlates with cysteine-rich protein 61 expression and poor prognosis in glioblastoma
title_full_unstemmed PIK3R1Met326Ile germline mutation correlates with cysteine-rich protein 61 expression and poor prognosis in glioblastoma
title_sort pik3r1met326ile germline mutation correlates with cysteine-rich protein 61 expression and poor prognosis in glioblastoma
publisher Nature Portfolio
publishDate 2017
url https://doaj.org/article/3e7ede37e22043e69e63784956e3a78e
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