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

• Published in: Clinical cancer research Vol. 11; no. 9; pp. 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
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01-05-2005
• 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; Malignant glioma; Nervous system diseases; Central nervous system disease; Glioblastoma; Radiation; Malignant tumor; Gene expression; Survival
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-04-1765

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.