Abstract
BackgroundKallikreins have clinical value as prognostic markers in a subset of malignancies examined to date, including kallikrein 3 (prostate specific antigen) in prostate cancer. We previously demonstrated that kallikrein 6 is expressed at higher levels in grade IV compared to grade III astrocytoma and is associated with reduced survival of GBM patients.MethodsIn this study we determined KLK1, KLK6, KLK7, KLK8, KLK9 and KLK10 protein expression in two independent tissue microarrays containing 60 grade IV and 8 grade III astrocytoma samples. Scores for staining intensity, percent of tumor stained and immunoreactivity scores (IR, product of intensity and percent) were determined and analyzed for correlation with patient survival.ResultsGrade IV glioma was associated with higher levels of kallikrein-immunostaining compared to grade III specimens. Univariable Cox proportional hazards regression analysis demonstrated that elevated KLK6- or KLK7-IR was associated with poor patient prognosis. In addition, an increased percent of tumor immunoreactive for KLK6 or KLK9 was associated with decreased survival in grade IV patients. Kaplan-Meier survival analysis indicated that patients with KLK6-IR < 10, KLK6 percent tumor core stained < 3, or KLK7-IR < 9 had a significantly improved survival. Multivariable analysis indicated that the significance of these parameters was maintained even after adjusting for gender and performance score.ConclusionsThese data suggest that elevations in glioblastoma KLK6, KLK7 and KLK9 protein have utility as prognostic markers of patient survival.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-015-1566-5) contains supplementary material, which is available to authorized users.
Highlights
IntroductionKallikreins have clinical value as prognostic markers in a subset of malignancies examined to date, including kallikrein 3 (prostate specific antigen) in prostate cancer
Kallikreins have clinical value as prognostic markers in a subset of malignancies examined to date, including kallikrein 3 in prostate cancer
In this regard it is of interest that are levels of KLK6 significantly elevated in high-grade glioma (glioblastoma multiforme (GBM), grade IV astrocytoma) and associated with poor patient survival, but in addition KLK6 promotes the resistance of glioma cells to a wide variety of cell deathinducing agents, including staurosporine, cisplatin, radiation and temozolomide [5]
Summary
Kallikreins have clinical value as prognostic markers in a subset of malignancies examined to date, including kallikrein 3 (prostate specific antigen) in prostate cancer. We previously demonstrated that kallikrein 6 is expressed at higher levels in grade IV compared to grade III astrocytoma and is associated with reduced survival of GBM patients. Expression levels of select kallikreins (KLK) are proposed or already used as biomarkers in human malignancies, including prostate, ovarian or breast cancers. Gain of chromosome 19 in glioblastoma has been correlated with a poor prognosis [10], an effect attributed to radiation resistance [11] In this regard it is of interest that are levels of KLK6 significantly elevated in high-grade glioma (glioblastoma multiforme (GBM), grade IV astrocytoma) and associated with poor patient survival, but in addition KLK6 promotes the resistance of glioma cells to a wide variety of cell deathinducing agents, including staurosporine, cisplatin, radiation and temozolomide [5]. Tumor KLK8 RNA expression in the same patient cohort was not associated with survival [13]
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