Fig. 1

NNI-STAT3 functionally tuned gene signature stratifies patient survival independent of current clinical indicators. a STAT3 co-expressed genes from Rembrandt patient database (middle panel) that displayed inverse expression upon STAT3 knockdown (KD) (left panel) were identified to form the NNI-STAT3 functionally tuned gene signature (right panel). b In Gravendeel clinical database, STAT3-high patient all glioma cohort was enriched in mesenchymal and classical molecular subtypes, with predominantly isocitrate dehydrogenase 1 (IDH)-wild-type status. STAT3-low tumors, in contrast, comprised mostly low-grade gliomas (LGGs), IDH-mutant (1p/19q co-deleted and non-co-deleted), and proneural molecular subtypes. c NNI-STAT3 signature stratified all glioma patient survival in Gravendeel clinical database. An enrichment of STAT3 pathway activation defined the poor prognosis patients (STAT3-high, 8.04 months), while patients of STAT3-low survived significantly longer (57.48 months). d A combination of NNI-STAT3 gene signature, World Health Organization status, Karnofsky (Karn) score, and age presented the best statistical model to account for the variability in patient survival, using the Bayesian Information Criterion (BIC) method. e NNI-STAT3 signature performed better than the existing Alvarez STAT3 signature for glioma patient prognosis. f The relative odds of correlation between STAT3 signature and IDH mutation is 2.42 in a diagnostic metrics test. Patients with a negative signature score (STAT3-high) are 2.42 times more likely to be IDH-wild-type than those with a positive signature score (STAT3-low). g STAT3-high GBM patient cohort was enriched in mesenchymal and classical molecular subtypes. STAT3-low tumors, in contrast, comprised mostly the proneural molecular subtype. h NNI-STAT3 signature stratified glioblastoma patient survival. An enrichment of STAT3 pathway activation defined the poor prognosis patients (STAT3-high, 7.1 months) while patients of STAT3-low survived significantly longer (12.4 months)