title: YKL-40 expression is associated with poorer response to radiation and shorter overall survival in glioblastoma.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
authors.affiliation: Department of Radiation Oncology, Neuro-Oncology, and Pathology, University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Christopher E
authors.initials: CE
authors.lastname: Pelloski
authors.forename: Anita
authors.initials: A
authors.lastname: Mahajan
authors.forename: Moshe
authors.initials: M
authors.lastname: Maor
authors.forename: Eric L
authors.initials: EL
authors.lastname: Chang
authors.forename: Shiao
authors.initials: S
authors.lastname: Woo
authors.forename: Mark
authors.initials: M
authors.lastname: Gilbert
authors.forename: Howard
authors.initials: H
authors.lastname: Colman
authors.forename: Helen
authors.initials: H
authors.lastname: Yang
authors.forename: Alicia
authors.initials: A
authors.lastname: Ledoux
authors.forename: Hilary
authors.initials: H
authors.lastname: Blair
authors.forename: Sandra
authors.initials: S
authors.lastname: Passe
authors.forename: Robert B
authors.initials: RB
authors.lastname: Jenkins
authors.forename: Kenneth D
authors.initials: KD
authors.lastname: Aldape
mesh_terms: D054392:Adipokines; D000328:Adult; D000368:Aged; D001921:Brain / Q000473:pathology / Q000528:radiation effects / Q000601:surgery; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000628:therapy; D000071451:Chitinase-3-Like Protein 1; D002869:Chromosome Aberrations; D002879:Chromosomes, Human, Pair 10 / Q000235:genetics; D003131:Combined Modality Therapy; D066246:ErbB Receptors / Q000235:genetics; D005260:Female; D005784:Gene Amplification; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma / Q000235:genetics / Q000378:metabolism* / Q000628:therapy; D006023:Glycoproteins / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D037102:Lectins; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011379:Prognosis; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D054392:Adipokines; C084533:CHI3L1 protein, human; D000071451:Chitinase-3-Like Protein 1; D006023:Glycoproteins; D037102:Lectins; D066246:ErbB Receptors