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 B, Aldape Kenneth D
Department of Radiation Oncology, Neuro-Oncology, and Pathology, University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA.
Clin Cancer Res. 2005 May 1;11(9):3326-34. doi: 10.1158/1078-0432.CCR-04-1765.
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.
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.
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.
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.
YKL-40是一种分泌蛋白，尽管其功能尚不清楚，但据报道它在上皮癌和神经胶质瘤中过表达。之前在一个较小样本集中的数据表明，YKL-40是与较差临床结果及胶质母细胞瘤一个基因定义亚组相关的标志物。在此，我们在更大系列的胶质母细胞瘤患者中验证这些发现，尤其是确定肿瘤YKL-40表达是否与放射反应相关。
对147例次全切除的患者在放射治疗后的系列研究中进行成像评估肿瘤大小的变化。另外一组140例接受了全切除的胶质母细胞瘤患者用于验证生存相关性，并将其扩展至残留疾病最少的患者。
在次全切除组中，较高的YKL-40表达与较差的放射反应、较短的进展时间和较短的总生存期显著相关。较高的YKL-40表达与较差生存的相关性在全切除组中得到验证。在两组合并的多变量分析中（n = 287），在调整患者年龄、功能状态和切除范围后，YKL-40是生存的独立预测因子。通过使用荧光原位杂交评估表皮生长因子受体扩增和10号染色体长臂缺失（这些肿瘤中两种常见的复发性畸变），还将YKL-40表达与胶质母细胞瘤的基因定义亚组进行了比较。YKL-40与10号染色体长臂缺失显著相关。
这些发现表明YKL-40是胶质母细胞瘤治疗反应和基因亚型的重要标志物，并提示它可能在这些肿瘤中发挥致癌作用。
