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YKL-40 Expression is Associated with Poorer Response to Radiation and Shorter Overall Survival in Glioblastoma

Purpose: YKL-40 is a secreted protein that has been reported to be overexpressed in epithelial cancers and gliomas, although its function is unknown. Previous data in a smaller sample set suggested that YKL-40 was a marker associated with a poorer clinical outcome and a genetically defined subgroup...

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Published in:Clinical cancer research 2005-05, Vol.11 (9), p.3326-3334
Main Authors: PELLOSKI, Christopher E, MAHAJAN, Anita, PASSE, Sandra, JENKINS, Robert B, ALDAPE, Kenneth D, MAOR, Moshe, CHANG, Eric L, SHIAO WOO, GILBERT, Mark, COLMAN, Howard, YANG, Helen, LEDOUX, Alicia, BLAIR, Hilary
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cited_by cdi_FETCH-LOGICAL-c3635-e4d3e1416d410225924ac2f654a63615c2f27730f702edcceb8279bc495ad853
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creator PELLOSKI, Christopher E
MAHAJAN, Anita
PASSE, Sandra
JENKINS, Robert B
ALDAPE, Kenneth D
MAOR, Moshe
CHANG, Eric L
SHIAO WOO
GILBERT, Mark
COLMAN, Howard
YANG, Helen
LEDOUX, Alicia
BLAIR, Hilary
description Purpose: YKL-40 is a secreted protein that has been reported to be overexpressed in epithelial cancers and gliomas, although its function is unknown. Previous data in a smaller sample set suggested that YKL-40 was a marker associated with a poorer clinical outcome and a genetically defined subgroup of glioblastoma. Here we test these findings in a larger series of patients with glioblastoma, and in particular, determine if tumor YKL-40 expression is associated with radiation response. Experimental Design: Patients ( n = 147) with subtotal resections were studied for imaging-assessed changes in tumor size in serial studies following radiation therapy. An additional set ( n = 140) of glioblastoma patients who underwent a gross-total resection was tested to validate the survival association and extend them to patients with minimal residual disease. Results: In the subtotal resection group, higher YKL-40 expression was significantly associated with poorer radiation response, shorter time to progression and shorter overall survival. The association of higher YKL-40 expression with poorer survival was validated in the gross-total resection group. In multivariate analysis with both groups combined ( n = 287), YKL-40 was an independent predictor of survival after adjusting for patient age, performance status, and extent of resection. YKL-40 expression was also compared with genetically defined subsets of glioblastoma by assessing epidermal growth factor receptor amplification and loss at chromosome 10q, two of the common recurring aberrations in these tumors, using fluorescent in situ hybridization. YKL-40 was significantly associated with 10q loss. Conclusions: The findings implicate YKL-40 as an important marker of therapeutic response and genetic subtype in glioblastomas and suggest that it may play an oncogenic role in these tumors.
doi_str_mv 10.1158/1078-0432.CCR-04-1765
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Previous data in a smaller sample set suggested that YKL-40 was a marker associated with a poorer clinical outcome and a genetically defined subgroup of glioblastoma. Here we test these findings in a larger series of patients with glioblastoma, and in particular, determine if tumor YKL-40 expression is associated with radiation response. Experimental Design: Patients ( n = 147) with subtotal resections were studied for imaging-assessed changes in tumor size in serial studies following radiation therapy. An additional set ( n = 140) of glioblastoma patients who underwent a gross-total resection was tested to validate the survival association and extend them to patients with minimal residual disease. Results: In the subtotal resection group, higher YKL-40 expression was significantly associated with poorer radiation response, shorter time to progression and shorter overall survival. The association of higher YKL-40 expression with poorer survival was validated in the gross-total resection group. In multivariate analysis with both groups combined ( n = 287), YKL-40 was an independent predictor of survival after adjusting for patient age, performance status, and extent of resection. YKL-40 expression was also compared with genetically defined subsets of glioblastoma by assessing epidermal growth factor receptor amplification and loss at chromosome 10q, two of the common recurring aberrations in these tumors, using fluorescent in situ hybridization. YKL-40 was significantly associated with 10q loss. Conclusions: The findings implicate YKL-40 as an important marker of therapeutic response and genetic subtype in glioblastomas and suggest that it may play an oncogenic role in these tumors.</description><identifier>ISSN: 1078-0432</identifier><identifier>EISSN: 1557-3265</identifier><identifier>DOI: 10.1158/1078-0432.CCR-04-1765</identifier><identifier>PMID: 15867231</identifier><language>eng</language><publisher>Philadelphia, PA: American Association for Cancer Research</publisher><subject>Adipokines ; Adult ; Aged ; Antineoplastic agents ; Biological and medical sciences ; Brain - pathology ; Brain - radiation effects ; Brain - surgery ; Brain Neoplasms - genetics ; Brain Neoplasms - metabolism ; Brain Neoplasms - therapy ; Chitinase-3-Like Protein 1 ; Chromosome Aberrations ; Chromosomes, Human, Pair 10 - genetics ; Combined Modality Therapy ; Female ; Gene Amplification ; Gene Expression Regulation, Neoplastic ; Glioblastoma - genetics ; Glioblastoma - metabolism ; Glioblastoma - therapy ; Glioma ; Glycoproteins - biosynthesis ; Glycoproteins - genetics ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Lectins ; Magnetic Resonance Imaging ; Male ; Medical sciences ; Middle Aged ; Multivariate Analysis ; Neurology ; Pharmacology. Drug treatments ; Prognosis ; prognostic marker ; Receptor, Epidermal Growth Factor - genetics ; Survival Analysis ; Treatment Outcome ; Tumors of the nervous system. Phacomatoses</subject><ispartof>Clinical cancer research, 2005-05, Vol.11 (9), p.3326-3334</ispartof><rights>2005 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3635-e4d3e1416d410225924ac2f654a63615c2f27730f702edcceb8279bc495ad853</citedby><cites>FETCH-LOGICAL-c3635-e4d3e1416d410225924ac2f654a63615c2f27730f702edcceb8279bc495ad853</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&amp;idt=16738063$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15867231$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>PELLOSKI, Christopher E</creatorcontrib><creatorcontrib>MAHAJAN, Anita</creatorcontrib><creatorcontrib>PASSE, Sandra</creatorcontrib><creatorcontrib>JENKINS, Robert B</creatorcontrib><creatorcontrib>ALDAPE, Kenneth D</creatorcontrib><creatorcontrib>MAOR, Moshe</creatorcontrib><creatorcontrib>CHANG, Eric L</creatorcontrib><creatorcontrib>SHIAO WOO</creatorcontrib><creatorcontrib>GILBERT, Mark</creatorcontrib><creatorcontrib>COLMAN, Howard</creatorcontrib><creatorcontrib>YANG, Helen</creatorcontrib><creatorcontrib>LEDOUX, Alicia</creatorcontrib><creatorcontrib>BLAIR, Hilary</creatorcontrib><title>YKL-40 Expression is Associated with Poorer Response to Radiation and Shorter Overall Survival in Glioblastoma</title><title>Clinical cancer research</title><addtitle>Clin Cancer Res</addtitle><description>Purpose: YKL-40 is a secreted protein that has been reported to be overexpressed in epithelial cancers and gliomas, although its function is unknown. Previous data in a smaller sample set suggested that YKL-40 was a marker associated with a poorer clinical outcome and a genetically defined subgroup of glioblastoma. Here we test these findings in a larger series of patients with glioblastoma, and in particular, determine if tumor YKL-40 expression is associated with radiation response. Experimental Design: Patients ( n = 147) with subtotal resections were studied for imaging-assessed changes in tumor size in serial studies following radiation therapy. An additional set ( n = 140) of glioblastoma patients who underwent a gross-total resection was tested to validate the survival association and extend them to patients with minimal residual disease. Results: In the subtotal resection group, higher YKL-40 expression was significantly associated with poorer radiation response, shorter time to progression and shorter overall survival. The association of higher YKL-40 expression with poorer survival was validated in the gross-total resection group. In multivariate analysis with both groups combined ( n = 287), YKL-40 was an independent predictor of survival after adjusting for patient age, performance status, and extent of resection. YKL-40 expression was also compared with genetically defined subsets of glioblastoma by assessing epidermal growth factor receptor amplification and loss at chromosome 10q, two of the common recurring aberrations in these tumors, using fluorescent in situ hybridization. YKL-40 was significantly associated with 10q loss. Conclusions: The findings implicate YKL-40 as an important marker of therapeutic response and genetic subtype in glioblastomas and suggest that it may play an oncogenic role in these tumors.</description><subject>Adipokines</subject><subject>Adult</subject><subject>Aged</subject><subject>Antineoplastic agents</subject><subject>Biological and medical sciences</subject><subject>Brain - pathology</subject><subject>Brain - radiation effects</subject><subject>Brain - surgery</subject><subject>Brain Neoplasms - genetics</subject><subject>Brain Neoplasms - metabolism</subject><subject>Brain Neoplasms - therapy</subject><subject>Chitinase-3-Like Protein 1</subject><subject>Chromosome Aberrations</subject><subject>Chromosomes, Human, Pair 10 - genetics</subject><subject>Combined Modality Therapy</subject><subject>Female</subject><subject>Gene Amplification</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Glioblastoma - genetics</subject><subject>Glioblastoma - metabolism</subject><subject>Glioblastoma - therapy</subject><subject>Glioma</subject><subject>Glycoproteins - biosynthesis</subject><subject>Glycoproteins - genetics</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>In Situ Hybridization, Fluorescence</subject><subject>Lectins</subject><subject>Magnetic Resonance Imaging</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Multivariate Analysis</subject><subject>Neurology</subject><subject>Pharmacology. Drug treatments</subject><subject>Prognosis</subject><subject>prognostic marker</subject><subject>Receptor, Epidermal Growth Factor - genetics</subject><subject>Survival Analysis</subject><subject>Treatment Outcome</subject><subject>Tumors of the nervous system. 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Previous data in a smaller sample set suggested that YKL-40 was a marker associated with a poorer clinical outcome and a genetically defined subgroup of glioblastoma. Here we test these findings in a larger series of patients with glioblastoma, and in particular, determine if tumor YKL-40 expression is associated with radiation response. Experimental Design: Patients ( n = 147) with subtotal resections were studied for imaging-assessed changes in tumor size in serial studies following radiation therapy. An additional set ( n = 140) of glioblastoma patients who underwent a gross-total resection was tested to validate the survival association and extend them to patients with minimal residual disease. Results: In the subtotal resection group, higher YKL-40 expression was significantly associated with poorer radiation response, shorter time to progression and shorter overall survival. The association of higher YKL-40 expression with poorer survival was validated in the gross-total resection group. In multivariate analysis with both groups combined ( n = 287), YKL-40 was an independent predictor of survival after adjusting for patient age, performance status, and extent of resection. YKL-40 expression was also compared with genetically defined subsets of glioblastoma by assessing epidermal growth factor receptor amplification and loss at chromosome 10q, two of the common recurring aberrations in these tumors, using fluorescent in situ hybridization. YKL-40 was significantly associated with 10q loss. 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ispartof Clinical cancer research, 2005-05, Vol.11 (9), p.3326-3334
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1557-3265
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source Freely Accessible Journals
subjects Adipokines
Adult
Aged
Antineoplastic agents
Biological and medical sciences
Brain - pathology
Brain - radiation effects
Brain - surgery
Brain Neoplasms - genetics
Brain Neoplasms - metabolism
Brain Neoplasms - therapy
Chitinase-3-Like Protein 1
Chromosome Aberrations
Chromosomes, Human, Pair 10 - genetics
Combined Modality Therapy
Female
Gene Amplification
Gene Expression Regulation, Neoplastic
Glioblastoma - genetics
Glioblastoma - metabolism
Glioblastoma - therapy
Glioma
Glycoproteins - biosynthesis
Glycoproteins - genetics
Humans
Immunohistochemistry
In Situ Hybridization, Fluorescence
Lectins
Magnetic Resonance Imaging
Male
Medical sciences
Middle Aged
Multivariate Analysis
Neurology
Pharmacology. Drug treatments
Prognosis
prognostic marker
Receptor, Epidermal Growth Factor - genetics
Survival Analysis
Treatment Outcome
Tumors of the nervous system. Phacomatoses
title YKL-40 Expression is Associated with Poorer Response to Radiation and Shorter Overall Survival in Glioblastoma
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