Construction and validation of a glioblastoma prognostic model based on immune-related genes

Abstract

BackgroundGlioblastoma multiforme (GBM) is a common malignant brain tumor with high mortality. It is urgently necessary to develop a new treatment because traditional approaches have plateaued.PurposeHere, we identified an immune-related gene (IRG)-based prognostic signature to comprehensively define the prognosis of GBM.MethodsGlioblastoma samples were selected from the Chinese Glioma Genome Atlas (CGGA). We retrieved IRGs from the ImmPort data resource. Univariate Cox regression and LASSO Cox regression analyses were used to develop our predictive model. In addition, we constructed a predictive nomogram integrating the independent predictive factors to determine the one-, two-, and 3-year overall survival (OS) probabilities of individuals with GBM. Additionally, the molecular and immune characteristics and benefits of ICI therapy were analyzed in subgroups defined based on our prognostic model. Finally, the proteins encoded by the selected genes were identified with liquid chromatography-tandem mass spectrometry and western blotting (WB).ResultsSix IRGs were used to construct the predictive model. The GBM patients were categorized into a high-risk group and a low-risk group. High-risk group patients had worse survival than low-risk group patients, and stronger positive associations with multiple tumor-related pathways, such as angiogenesis and hypoxia pathways, were found in the high-risk group. The high-risk group also had a low IDH1 mutation rate, high PTEN mutation rate, low 1p19q co-deletion rate and low MGMT promoter methylation rate. In addition, patients in the high-risk group showed increased immune cell infiltration, more aggressive immune activity, higher expression of immune checkpoint genes, and less benefit from immunotherapy than those in the low-risk group. Finally, the expression levels of TNC and SSTR2 were confirmed to be significantly associated with patient prognosis by protein mass spectrometry and WB.ConclusionHerein, a robust predictive model based on IRGs was developed to predict the OS of GBM patients and to aid future clinical research.

Investigating the effects of PTEN mutations on cGAS-STING pathway in glioblastoma tumours

“…This study shows that expression of cGAS-STING pathway members like STING, revealed that patients with PTEN mutation are in the highrisk group [21]. Increased immune cell infiltration, more aggressive immune activity, higher expression of immune checkpoint genes, and less benefit from immunotherapy are listed among the characteristic features of these high-risk group patients [21]. These results are also in accordance with the PTEN-associated immune prognostic signature in GBM [22,23].…”

“…Therefore, mutation-dependent gain or loss of function of phosphatase activity might have potential effects on interferon release. This study shows that expression of cGAS-STING pathway members like STING, revealed that patients with PTEN mutation are in the highrisk group [21]. Increased immune cell infiltration, more aggressive immune activity, higher expression of immune checkpoint genes, and less benefit from immunotherapy are listed among the characteristic features of these high-risk group patients [21].…”

Disease-Based Prognostication: Neuro-Oncology

“…Studies have implicated MSH2, which plays a key role in DNA mismatch repair, as having a potential predictive role, 50 as well as immune-related genes. 51,52 Male glioblastoma patients have a lower OS compared with women. [53][54][55] A retrospective, secondary study utilizing data from NRG Oncology RTOG trials developed and independently validated prognostic nomograms which take sex into consideration.…”