Abstract
Abstract BACKGROUND Craniopharyngiomas are rare, low histologic grade neoplasms of the suprasellar region. Despite their benign histology, these tumors can be challenging to manage due to the morbidities associated with surgery or radiation and their tendency to recur after treatment. In this study, we set out to identify transcriptional factors that may influence or predict recurrence. METHODS We analyzed RNA-sequencing data of 77 craniopharyngioma tissue samples from the Open Pediatric Brain Tumor Atlas cohort and corresponding clinical data. Kaplan-Meier survival analysis was performed using R. Differential expression analysis and gene set enrichment analysis (GSEA) of hallmark pathways was performed. RESULTS The transcription factor NKX3.1 was found to be markedly upregulated in craniopharyngioma relative to other brain tumor histologies (p<0.05). NKX3.1 is a well-studied tumor suppressor in prostate cancer and its reduction or loss of expression is seen with disease progression. Patients with higher NKX3.1 expression had better event-free survival (p=0.0049) and had an average of 530 days longer event-free survival (p=0.036). There was no statistically significant difference in age, sex, tumor location, and extent of tumor resection between high and low NKX3.1 expression groups. There was no significant difference in overall survival (p=0.23). GSEA revealed that patients with high NKX3.1 expression had decreased activation of the Epithelial-Mesenchymal Transition pathway (NES=-1.84, adj. p<0.001) and reduced activation of inflammatory pathways, including the complement, inflammatory response, and IL6-JAK-STAT3 pathways (NES<-1.6, adj. p<0.001). CONCLUSION These findings reveal NKX3.1 as a potential prognostic marker for craniopharyngioma recurrence. Low NKX3.1 expression also correlated with inflammatory pathway activation, a factor that has been previously associated with more aggressive behavior and worse prognosis. Future work is planned to validate NKX3.1 protein expression in patient specimens.
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