Overexpression of IGFBP2 mRNA predicts poor survival in patients with glioblastoma

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.

Large-Scale Analysis Reveals Gene Signature for Survival Prediction in Primary Glioblastoma

“…VM has been considered as one of the reasons that GBM becomes resistant to anti-VEGF therapy [ 30 ]. Our study confirmed significant up-regulation of IGFBP2 and predicted a poor outcome for patients as shown in previous studies [ 17 , 31 – 33 ], thus providing more evidence for further research into its functional roles during GBM progression. PTPRN is also located on the human chromosome 2 (2q35) but is interestingly down-regulated in GBM tissue and was associated with poor prognosis as the expression increased.…”

Expanding the scope of candidate prognostic marker IGFBP2 in glioblastoma

“…Innovative technologies could present more robust and reliable data leading to, for example revival and repurposing of ‘forgotten’ biomarkers. In the present study, RNAscope probe was used to detect the expression of IGFBP2 mRNA in 180 glioblastomas [11]. The analysis revealed 16.9 months median overall survival for the patients with low IGFBP2 mRNA levels, but only 11.6 months for patients with high IGFBP2 , which is a striking difference.…”

“…Following a previous comparison of gene expression profiles between gliomas with different grades that revealed frequent overexpression of insulin-like growth factor binding protein 2 ( IGFBP2 ) in glioblastomas [12], Yuan et al [11] set out to investigate IGFPB2 mRNA levels in a larger cohort of glioblastomas. What is known about IGFBP2 in brain tumors?…”

“…As mentioned, IGFBP2 overexpression is common in high-grade glioma and IGFBP2 is a prognostic factor for poor survival [17]. One may wonder why Yuan et al [11] set out to re-investigate something already known nearly two decades ago [12]. Well, the answer is that studies of IGFBP2 transcript expression in glioblastoma biopsies detected by an in situ method were very few, but as of today, the techniques have been improved and could either confirm or challenge previous results.…”

“…It is of further interest to test IGFBP2 levels and its prognostic value on to already established biomarkers since it may, for example, help to select patients with poor prognosis and who may benefit from more rapid or aggressive therapy. Yuan et al [11] therefore divided the glioblastoma patients into subgroups. Combining IGFBP2 mRNA expression and TERT promoter status, the survival analysis showed that GBM patients harboring wild-type TERT promoter had the longest median overall survival time of 19.6 months.…”