Evaluating STAT5 Signature in Recurrent Glioblastoma

Background: Recurrent glioblastoma (GBM) is resistant to available treatments and continued growth of the tumor is inevitable; this process is facilitated by the expression of genes regulated by the Signal Transducer and Activator of Transcription (STAT) family of transcription factors, namely STAT5, active in the invasive rim of GBM tumors. Currently, there are no targeted therapies for recurrent GBM that increase the overall patient survival rate. This study aims to analyze the differential expression of genes regulated by STAT5 between primary and recurrent GBM.<br/>Methods: Analysis of whole exome and RNA sequencing were performed on matched bulk primary and multiple recurrent tumor samples from GBM patients who received the current standard care to determine significant changes in gene expression of STAT3/5 targets. <br/>Results: Statistical analysis reveals a decrease in Synaptotagmin 2 (SYT2) and Pleckstrin Homology Domain Containing A3 (PLEKHA3) at recurrence, previously identified as potential STAT5 targets. <br/>Conclusions: To get a better understanding of the roles of STAT5 in GBM recurrence, their downstream effects need to be better understood. The transcriptomic program initiated by STAT5 activation is distinct from that of STAT3 activation. The roles of STAT5 target genes in GBM are poorly characterized, so further research should focus on understanding the effects of altered expression of these genes as they relate to STAT3/5 in GBM recurrence.