Abstract
BackgroundGlioblastoma multiforme (GBM) is the most aggressive and frequent brain tumor, albeit without cure. Although patient survival is limited to one year on average, significant variability in outcome is observed. The assessment of biomarkers is needed to gain better knowledge of this type of tumor, help prognosis, design and evaluate therapies. The neurodevelopmental polysialic acid neural cell adhesion molecule (PSA-NCAM) protein is overexpressed in various cancers. Here, we studied its expression in GBM and evaluated its prognosis value for overall survival (OS) and disease free survival (DFS).MethodsWe set up a specific and sensitive enzyme linked immunosorbent assay (ELISA) test for PSA-NCAM quantification, which correlated well with PSA-NCAM semi quantitative analysis by immunohistochemistry, and thus provides an accurate quantitative measurement of PSA-NCAM content for the 56 GBM biopsies analyzed. For statistics, the Spearman correlation coefficient was used to evaluate the consistency between the immunohistochemistry and ELISA data. Patients' survival was estimated by using the Kaplan-Meier method, and curves were compared using the log-rank test. On multivariate analysis, the effect of potential risk factors on the DFS and OS were evaluated using the cox regression proportional hazard models. The threshold for statistical significance was p = 0.05.ResultsWe showed that PSA-NCAM was expressed by approximately two thirds of the GBM at variable levels. On univariate analysis, PSA-NCAM content was an adverse prognosis factor for both OS (p = 0.04) and DFS (p = 0.0017). On multivariate analysis, PSA-NCAM expression was an independent negative predictor of OS (p = 0.046) and DFS (p = 0.007). Furthermore, in glioma cell lines, PSA-NCAM level expression was correlated to the one of olig2, a transcription factor required for gliomagenesis.ConclusionPSA-NCAM represents a valuable biomarker for the prognosis of GBM patients.
Highlights
Glioblastoma multiforme (GBM) is the most aggressive and frequent brain tumor, albeit without cure
We have reported that olig2 is expressed by all human gliomas whatever their subtype and grade [10], but its level is dramatically increased in highly proliferative, tumorigenic GBM cell lines [11]
PSA-NCAM regulates olig2 expression in glioma To further elucidate the role that PSA-NCAM could play in GB, we investigated whether PSA removal using endoN affected the properties of the GBM9 cell line we previously developed and characterized as a highly proliferative neurosphere forming cell line [9]
Summary
Glioblastoma multiforme (GBM) is the most aggressive and frequent brain tumor, albeit without cure. Patient survival is limited to one year on average, significant variability in outcome is observed. The assessment of biomarkers is needed to gain better knowledge of this type of tumor, help prognosis, design and evaluate therapies. We studied its expression in GBM and evaluated its prognosis value for overall survival (OS) and disease free survival (DFS). Progress in GBM treatment has been limited. One of the main impediments to long-term survival is recurrence despite resection of the primary tumor. To date, the main significant prognosis factors evaluated in large cohorts of patients are O6-methylguanine-DNA methyl transferase promoter methylation status, age, extent of resection, performance status, and mini mental state examination [4]
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