Fig 1.
Modeling of protein expression (H-score) cutoffs for low vs. high protein expression.
Each curve reports the score of a Cox Proportional Hazards model associated with different cut-off values of the related protein expression to bin scores into Low versus High expression. Protein expression is measured as the H score rescaled to (0–3). Optimal cut-offs are identified as the mode in the cut-off vs. score curve. For VEGFA, this was not identifiable and an 80th percentile H-score was used as a cut-off.
Fig 2.
Representative outputs of Probe Set Analyzer for selected molecular signatures of TRGC.
A real-time correlation of patient survival and gene expression levels of selected signatures of TRGC was performed using Probe Set Analyzer (http://probesetanalyzer.com/index.aspx). “Newly Diagnosed", “Recurrent" or “combined all tumors” were analyzed. The y-axis represents normalized gene expression intensity, and the x-axis represents patient groups. The sliding bars position patients into high, mid and low gene expression level groups. A Kaplan-Meier curve with corresponding p-values is generated based on each change to these patient groups. An integrated statistical engine calculated p-values based on Kaplan-Meier curves.
Fig 3.
Kaplan-Meier survival curves for newly diagnosed and recurrent GBMs expressed differential levels of selected signatures of TRGC.
These survival curves for RPS11, RPS20, and VEGFA correspond to the Cox Proportional Hazards data in Table 1. Both primary and secondary GBMs were included in the analyses.
Fig 4.
Upregulation of protein levels of TRGC signatures in GBM subgroups correlates with patients' poor prognosis.
Representative immunohistochemical staining of RPS11 and RPS20 in clinical GBM subgroups. Upregulation of RPS11 was found to increase the hazard of death (HOD) 11-fold in newly diagnosed primary GBM (a, b) (Table 2) and 7-fold in a secondary GBM (c, d) (S2 Table). Upregulation of RPS20 was found to increase the HOD 5-fold in newly diagnosed primary GBM (e, f) (Table 2). The survival times of each representative patient are shown.
Table 1.
Tissue microarray protein expression- Cox proportional hazard analysis (primary and secondary GBMs included).
Table 2.
Tissue microarray protein expression- Cox proportional hazard analysis (primary GBMs only).
Table 3.
Correlation with poor survival in newly diagnosed and recurrent GBMs (primary and secondary GBMs included).
Fig 5.
Correlations of the expression level of RPS11, the status of MGMT methylation, IDH mutation and age with patient survival.
Each indicated factor was analyzed as an independent prognostic factor. Changes in relative risk were depicted with Kaplan-Meier curves and analyzed using log-rank tests.
Table 4.
TCGA analysis—correlation with poor survival in newly diagnosed primary GBMs.