YKL-40 expression is associated with poorer response to radiation and shorter overall survival in glioblastoma.
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.
Pelloski
Christopher E
CE
Department of Radiation Oncology, Neuro-Oncology, and Pathology, University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA.
Mahajan
Anita
A
Maor
Moshe
M
Chang
Eric L
EL
Woo
Shiao
S
Gilbert
Mark
M
Colman
Howard
H
Yang
Helen
H
Ledoux
Alicia
A
Blair
Hilary
H
Passe
Sandra
S
Jenkins
Robert B
RB
Aldape
Kenneth D
KD
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
D054392:Adipokines; C084533:CHI3L1 protein, human; D000071451:Chitinase-3-Like Protein 1; D006023:Glycoproteins; D037102:Lectins; D066246:ErbB Receptors