The Mesenchymal glioblastoma subgroup contains the most frequent number of mutations in the NF1 tumor suppressor gene (37 percent). Frequent mutations in the PTEN and TP53 tumor suppressor genes also occurred in the group. Patients in the Mesenchymal group had significant increases in survival after aggressive treatment, unlike those in the Proneural, and to an extent, in the Neural subgroups.
Signal transducer and activator of transcription 3 (STAT3), a critical transcriptional activator in tumorigenesis, is persistently phosphorylated and associated with an unfavorable prognosis in glioblastoma multiforme (GBM). Although a set of specific targets has been identified, there have been no systematic analyses of STAT3 signaling based on GBM subtype.
A study compared STAT3-associated messenger RNA, protein, and microRNA expression profiles across different subtypes of GBM.
The analyses revealed a prominent role for STAT3 in the mesenchymal but not in other GBM subtypes, which can be reliably used to classify patients with mesenchymal GBM into 2 groups according to phosphorylated STAT3 expression level. Differentially expressed genes suggest an association between Notch signaling pathway and STAT3 signaling in the mesenchymal subtype. Their association was validated in the U87 cell, a malignant glioma cell line annotated as mesenchymal subtype. Specific associated proteins and microRNAs further profile the STAT3 signaling among GBM subtypes.
These findings suggest a prominent role for STAT3 signaling in mesenchymal glioblastoma (GBM) and highlight the importance of identifying signaling pathways that contribute to specific cancer subtypes 1).