Abstract
The prognosis of patients with glioblastoma (GBM) is dismal. It has been reported that Insulin-like growth factor (IGF) binding protein 2 (IGFBP2) is associated with the mobility and invasion of tumor cells. We investigated the expression of IGFBP2 mRNA in GBMs and its clinical relevance, using tissue microarrays and RNAscope in situ hybridization in 180 GBMs and 13 normal or edematous tissues. The correlations between the expression and clinical pathological parameters as well as some other biomarkers were analyzed. Overexpression of IGFBP2 mRNA was observed in 23.9% of tumors tested. No expression of IGFBP2 mRNA was detected in normal or edematous tissues. Kaplan–Meier survival analysis showed that the survival time of all the patients with high IGFBP2 tumors had shorter survival than those with low IGFBP2 (P<0.01). Univariate regression and multivariate regression both indicated that the expression of IGFBP2 transcript level was an independent prognostic factor (P=0.008 and 0.007, respectively). Furthermore, expression of IGFBP2 mRNA was related to the occurrence of isocitrate dehydrogenase 1 (IDH1) mutation, high heat shock protein 27 (Hsp27) expression and telomerase reverse transcriptase (TERT) promoter mutation (TERTp+) (P=0.013, 0.015 and 0.016, respectively), and patients with TERTp+/IGFBP2high showed the shortest survival. In conclusion, IGFBP2 mRNA expression status is an independent prognostic biomarker in GBMs, and the combination of IGFBP2 mRNA and TERTp status might serve as a prognostic indicator in patients with GBM.
Highlights
Glioblastomas (GBMs), as WHO IV gliomas, are the most aggressive primary brain malignancy in adults [1]
We examined the relationship between IGF binding protein 2 (IGFBP2) transcript level and clinic-pathological features
Previous studies [20] and the present study all demonstrated that IGFBP2 mRNA is highly expressed in GBM and strongly related to clinical parameters of patients, which suggested that IGFBP2 might be involved in maintenance of malignant phenotypes in GBM cells
Summary
Glioblastomas (GBMs), as WHO IV gliomas, are the most aggressive primary brain malignancy in adults [1]. Great anatomical and molecular heterogeneity within GBM bulk tumor could result in resistance to drug and radiation [3]. Previous clinical studies demonstrated that concurrent radio-chemotherapy and followed chemotherapy after surgical removal of the tumor has greater clinical efficacy than traditional therapy. The therapeutic regimen has become the standard treatment for GBMs. patients suffering from GBMs still have a dismal prognosis with a median overall survival (OS) of 15–17 months in clinical management [4,5,6]. An understanding of the molecular alterations of gliomas is critical for improving clinical management for patients with this disease
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