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High cytoplasmic FOXO1 and pFOXO1 expression in astrocytomas are associated with worse surgical outcome

FOXO1 is at a convergence point of receptor tyrosine kinase (RTK) signaling, which is one of the three core pathways implicated in glioblastoma. It was recently shown that FOXO1 can effectively induce glioma cell death and inhibit tumor growth through cell cycle arrest and apoptosis. We therefore ev...

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Published in:PloS one 2013-07, Vol.8 (7), p.e69260-e69260
Main Authors: Chen, Chao, Xu, Tao, Zhou, Jinxu, Yan, Yong, Li, Weiqing, Yu, Hongyu, Hu, Guohan, Ding, Xuehua, Chen, Juxiang, Lu, Yicheng
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cited_by cdi_FETCH-LOGICAL-c692t-f403ed347a1e801dc9f9211a648d15c3a5710c228870706f41596c5d17ed61b73
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description FOXO1 is at a convergence point of receptor tyrosine kinase (RTK) signaling, which is one of the three core pathways implicated in glioblastoma. It was recently shown that FOXO1 can effectively induce glioma cell death and inhibit tumor growth through cell cycle arrest and apoptosis. We therefore evaluated FOXO1 and pFOXO1 protein expression in 181 primary astrocytoma samples and 16 normal brain samples. Astrocytoma samples expressed higher cytoplasmic FOXO1 and pFOXO1 than normal brain samples. Nuclear pFOXO1 level was significantly higher than nuclear FOXO1 in astrocytomas. High cytoplasmic FOXO1 expression was associated with older onset age (P = 0.001) and higher WHO grade (P = 0.001). The trend was also observed between cytoplasmic pFOXO1 expression and WHO grade although not significant. Univariate survival analysis showed that both high cytoplasmic FOXO1 and pFOXO1 expression indicated a significantly shorter median overall survival and progression-free survival. Multivariate survival analysis revealed cytoplasmic FOXO1 expression, cytoplasmic pFOXO1 expression, WHO grade, gender, extent of resection and radiotherapy to be independent prognostic factors for overall survival and progression-free survival. Thus, our data suggested that cytoplasmic FOXO1 and pFOXO1 expression may serve as valuable prognostic variables in astrocytomas and may have significant implications for the development and application of targeted therapy.
doi_str_mv 10.1371/journal.pone.0069260
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Multivariate survival analysis revealed cytoplasmic FOXO1 expression, cytoplasmic pFOXO1 expression, WHO grade, gender, extent of resection and radiotherapy to be independent prognostic factors for overall survival and progression-free survival. 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expression in astrocytomas are associated with worse surgical outcome</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2013-07-09</date><risdate>2013</risdate><volume>8</volume><issue>7</issue><spage>e69260</spage><epage>e69260</epage><pages>e69260-e69260</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>FOXO1 is at a convergence point of receptor tyrosine kinase (RTK) signaling, which is one of the three core pathways implicated in glioblastoma. It was recently shown that FOXO1 can effectively induce glioma cell death and inhibit tumor growth through cell cycle arrest and apoptosis. We therefore evaluated FOXO1 and pFOXO1 protein expression in 181 primary astrocytoma samples and 16 normal brain samples. Astrocytoma samples expressed higher cytoplasmic FOXO1 and pFOXO1 than normal brain samples. Nuclear pFOXO1 level was significantly higher than nuclear FOXO1 in astrocytomas. High cytoplasmic FOXO1 expression was associated with older onset age (P = 0.001) and higher WHO grade (P = 0.001). The trend was also observed between cytoplasmic pFOXO1 expression and WHO grade although not significant. Univariate survival analysis showed that both high cytoplasmic FOXO1 and pFOXO1 expression indicated a significantly shorter median overall survival and progression-free survival. Multivariate survival analysis revealed cytoplasmic FOXO1 expression, cytoplasmic pFOXO1 expression, WHO grade, gender, extent of resection and radiotherapy to be independent prognostic factors for overall survival and progression-free survival. Thus, our data suggested that cytoplasmic FOXO1 and pFOXO1 expression may serve as valuable prognostic variables in astrocytomas and may have significant implications for the development and application of targeted therapy.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>23874926</pmid><doi>10.1371/journal.pone.0069260</doi><tpages>e69260</tpages><oa>free_for_read</oa></addata></record>
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subjects Adult
Aged
Analysis
Apoptosis
Astrocytoma
Astrocytoma - diagnosis
Astrocytoma - metabolism
Astrocytoma - mortality
Astrocytoma - surgery
Astrocytomas
Autophagy
Biology
Brain
Brain - metabolism
Brain cancer
Brain Neoplasms - diagnosis
Brain Neoplasms - metabolism
Brain Neoplasms - mortality
Brain Neoplasms - surgery
Brain tumors
Cancer therapies
Cell cycle
Cell death
Cyclin-dependent kinases
Cytoplasm - metabolism
Data processing
Development and progression
Female
Forkhead Box Protein O1
Forkhead Transcription Factors - metabolism
FOXO1 protein
Gastric cancer
Glioblastoma
Glioma
Glioma cells
Hospitals
Humans
Kinases
Male
Medical prognosis
Medicine
Middle Aged
Neoplasm Grading
Neoplasm Staging
Neurosurgery
Pathology
Phosphorylation
Prognosis
Prostate cancer
Protein-tyrosine kinase receptors
Quality
Radiation therapy
Signaling
Stomach cancer
Studies
Surgery
Survival
Transcription factors
Treatment Outcome
Tyrosine
title High cytoplasmic FOXO1 and pFOXO1 expression in astrocytomas are associated with worse surgical outcome
url http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-29T20%3A05%3A26IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=High%20cytoplasmic%20FOXO1%20and%20pFOXO1%20expression%20in%20astrocytomas%20are%20associated%20with%20worse%20surgical%20outcome&rft.jtitle=PloS%20one&rft.au=Chen,%20Chao&rft.date=2013-07-09&rft.volume=8&rft.issue=7&rft.spage=e69260&rft.epage=e69260&rft.pages=e69260-e69260&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0069260&rft_dat=%3Cgale_plos_%3EA478358113%3C/gale_plos_%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c692t-f403ed347a1e801dc9f9211a648d15c3a5710c228870706f41596c5d17ed61b73%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=1974584009&rft_id=info:pmid/23874926&rft_galeid=A478358113&rfr_iscdi=true