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

Abstract

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.

High VEGFA Expression Is Associated with Improved Progression-Free Survival after Bevacizumab Treatment in Recurrent Glioblastoma

“…Our results showed YKL40 to be highly expressed in tumor cells, consistent with previous reports [ 36 , 37 , 38 ]. Inflammatory cells also showed some expression of YKL40, which has been previously attributed to the presence of tumor-infiltrating macrophages [ 22 , 64 ].…”

“…In our evaluation of YKL40, 28 out of 55 (50.9%) samples had a low percentage of positive YKL40 tumor cells (<25%), while 12 out of 55 (21.8%) had a high percentage (>75%) ( Table 4 ). The majority of YKL40 expression (70.9%) was observed to be strong (and cytoplasmatic) ( Figure 1 g,h), as has been previously reported [ 36 , 37 , 38 ]. Moreover, YKL40 expression was observed, albeit to a lesser extent, in inflammatory cells.…”

High VEGFA Expression Is Associated with Improved Progression-Free Survival after Bevacizumab Treatment in Recurrent Glioblastoma

“…Our results showed YKL40 to be highly expressed in tumor cells, consistent with previous reports [ 36 , 37 , 38 ]. Inflammatory cells also showed some expression of YKL40, which has been previously attributed to the presence of tumor-infiltrating macrophages [ 22 , 64 ].…”

“…In our evaluation of YKL40, 28 out of 55 (50.9%) samples had a low percentage of positive YKL40 tumor cells (<25%), while 12 out of 55 (21.8%) had a high percentage (>75%) ( Table 4 ). The majority of YKL40 expression (70.9%) was observed to be strong (and cytoplasmatic) ( Figure 1 g,h), as has been previously reported [ 36 , 37 , 38 ]. Moreover, YKL40 expression was observed, albeit to a lesser extent, in inflammatory cells.…”

Prognostic implications of immunohistochemically detected YKL-40 expression in breast cancer

“…We noted cytoplasmic localization of the antigen within tumor cells, a finding consistent with that reported in a similar study of glioblastomas [10] and a previous survey of breast cancers [30]. This seems consistent with the fact that YKL-40 is a secreted protein and has been detected in sera of cancer patients.…”

YKL-40 expression in soft-tissue sarcomas and atypical lipomatous tumors

“…This suggests that YKL-40 expression in STS might be used as a prognostic factor for survival. This study is, however, too small to provide solid evidence, but our finding is similar to the results of other studies of YKL-40 expression in other tumors: glioblastomas (Pelloski et al 2005), epithelial ovarian cancer (Yang et al 2009), and gastric cancer (Bi et al 2009) with an association between YKL-40 expression and shorter survival. Other studies have established that tumor expression of YKL-40 is related to stage and histology, but has no correlation to overall survival (Roslind et al 2008, Høgdall et al 2009, Shao et al 2009).…”

High VEGFA Expression Is Associated with Improved Progression-Free Survival after Bevacizumab Treatment in Recurrent Glioblastoma

“…Our results showed YKL40 to be highly expressed in tumor cells, consistent with previous reports [ 36 , 37 , 38 ]. Inflammatory cells also showed some expression of YKL40, which has been previously attributed to the presence of tumor-infiltrating macrophages [ 22 , 64 ].…”

“…In our evaluation of YKL40, 28 out of 55 (50.9%) samples had a low percentage of positive YKL40 tumor cells (<25%), while 12 out of 55 (21.8%) had a high percentage (>75%) ( Table 4 ). The majority of YKL40 expression (70.9%) was observed to be strong (and cytoplasmatic) ( Figure 1 g,h), as has been previously reported [ 36 , 37 , 38 ]. Moreover, YKL40 expression was observed, albeit to a lesser extent, in inflammatory cells.…”

Prognostic implications of immunohistochemically detected YKL-40 expression in breast cancer

“…We noted cytoplasmic localization of the antigen within tumor cells, a finding consistent with that reported in a similar study of glioblastomas [10] and a previous survey of breast cancers [30]. This seems consistent with the fact that YKL-40 is a secreted protein and has been detected in sera of cancer patients.…”

YKL-40 expression in soft-tissue sarcomas and atypical lipomatous tumors

“…This suggests that YKL-40 expression in STS might be used as a prognostic factor for survival. This study is, however, too small to provide solid evidence, but our finding is similar to the results of other studies of YKL-40 expression in other tumors: glioblastomas (Pelloski et al 2005), epithelial ovarian cancer (Yang et al 2009), and gastric cancer (Bi et al 2009) with an association between YKL-40 expression and shorter survival. Other studies have established that tumor expression of YKL-40 is related to stage and histology, but has no correlation to overall survival (Roslind et al 2008, Høgdall et al 2009, Shao et al 2009).…”

High VEGFA Expression Is Associated with Improved Progression-Free Survival after Bevacizumab Treatment in Recurrent Glioblastoma

“…Our results showed YKL40 to be highly expressed in tumor cells, consistent with previous reports [ 36 , 37 , 38 ]. Inflammatory cells also showed some expression of YKL40, which has been previously attributed to the presence of tumor-infiltrating macrophages [ 22 , 64 ].…”

“…In our evaluation of YKL40, 28 out of 55 (50.9%) samples had a low percentage of positive YKL40 tumor cells (<25%), while 12 out of 55 (21.8%) had a high percentage (>75%) ( Table 4 ). The majority of YKL40 expression (70.9%) was observed to be strong (and cytoplasmatic) ( Figure 1 g,h), as has been previously reported [ 36 , 37 , 38 ]. Moreover, YKL40 expression was observed, albeit to a lesser extent, in inflammatory cells.…”

Prognostic implications of immunohistochemically detected YKL-40 expression in breast cancer

“…We noted cytoplasmic localization of the antigen within tumor cells, a finding consistent with that reported in a similar study of glioblastomas [10] and a previous survey of breast cancers [30]. This seems consistent with the fact that YKL-40 is a secreted protein and has been detected in sera of cancer patients.…”

YKL-40 expression in soft-tissue sarcomas and atypical lipomatous tumors

“…This suggests that YKL-40 expression in STS might be used as a prognostic factor for survival. This study is, however, too small to provide solid evidence, but our finding is similar to the results of other studies of YKL-40 expression in other tumors: glioblastomas (Pelloski et al 2005), epithelial ovarian cancer (Yang et al 2009), and gastric cancer (Bi et al 2009) with an association between YKL-40 expression and shorter survival. Other studies have established that tumor expression of YKL-40 is related to stage and histology, but has no correlation to overall survival (Roslind et al 2008, Høgdall et al 2009, Shao et al 2009).…”