YKL-40 expression is associated with poorer response to radiation and shorter overall survival in glioblastoma

Christopher E. Pelloski, Anita Mahajan, Moshe Maor, Eric L. Chang, Shiao Woo, Mark Gilbert, Howard Colman, Helen Yang, Alicia Ledoux, Hilary Blair, Sandra Passe, Robert Brian Jenkins, Kenneth D. Aldape

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Abstract

Purpose: YKL-40 is a secreted protein that has been reported to be overexpressed in epithelial cancers and gliomas, although its function its unknown. Previous data in a smaller samples 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 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.

Original languageEnglish (US)
Pages (from-to)3326-3334
Number of pages9
JournalClinical Cancer Research
Volume11
Issue number9
DOIs
StatePublished - May 1 2005

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Glioblastoma
Radiation
Survival
Neoplasms
Residual Neoplasm
Fluorescence In Situ Hybridization
Epidermal Growth Factor Receptor
Glioma
Research Design
Radiotherapy
Multivariate Analysis
Chromosomes
Proteins
Therapeutics

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Pelloski, C. E., Mahajan, A., Maor, M., Chang, E. L., Woo, S., Gilbert, M., ... Aldape, K. D. (2005). YKL-40 expression is associated with poorer response to radiation and shorter overall survival in glioblastoma. Clinical Cancer Research, 11(9), 3326-3334. https://doi.org/10.1158/1078-0432.CCR-04-1765

YKL-40 expression is associated with poorer response to radiation and shorter overall survival in glioblastoma. / Pelloski, Christopher E.; Mahajan, Anita; Maor, Moshe; Chang, Eric L.; Woo, Shiao; Gilbert, Mark; Colman, Howard; Yang, Helen; Ledoux, Alicia; Blair, Hilary; Passe, Sandra; Jenkins, Robert Brian; Aldape, Kenneth D.

In: Clinical Cancer Research, Vol. 11, No. 9, 01.05.2005, p. 3326-3334.

Research output: Contribution to journalArticle

Pelloski, CE, Mahajan, A, Maor, M, Chang, EL, Woo, S, Gilbert, M, Colman, H, Yang, H, Ledoux, A, Blair, H, Passe, S, Jenkins, RB & Aldape, KD 2005, 'YKL-40 expression is associated with poorer response to radiation and shorter overall survival in glioblastoma', Clinical Cancer Research, vol. 11, no. 9, pp. 3326-3334. https://doi.org/10.1158/1078-0432.CCR-04-1765
Pelloski, Christopher E. ; Mahajan, Anita ; Maor, Moshe ; Chang, Eric L. ; Woo, Shiao ; Gilbert, Mark ; Colman, Howard ; Yang, Helen ; Ledoux, Alicia ; Blair, Hilary ; Passe, Sandra ; Jenkins, Robert Brian ; Aldape, Kenneth D. / YKL-40 expression is associated with poorer response to radiation and shorter overall survival in glioblastoma. In: Clinical Cancer Research. 2005 ; Vol. 11, No. 9. pp. 3326-3334.
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AU - Pelloski, Christopher E.

AU - Mahajan, Anita

AU - Maor, Moshe

AU - Chang, Eric L.

AU - Woo, Shiao

AU - Gilbert, Mark

AU - Colman, Howard

AU - Yang, Helen

AU - Ledoux, Alicia

AU - Blair, Hilary

AU - Passe, Sandra

AU - Jenkins, Robert Brian

AU - Aldape, Kenneth D.

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N2 - Purpose: YKL-40 is a secreted protein that has been reported to be overexpressed in epithelial cancers and gliomas, although its function its unknown. Previous data in a smaller samples 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 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.

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