Abstract
BACKGROUND
Medulloblastoma is an aggressive pediatric brain tumor with surgery and post-resection radiotherapy plus chemotherapy as the major type of treatment currently.
METHODS
A cohort of 52 medulloblastoma patients were treated in Taipei Medical University Hospital and Taipei Veterans General Hospital. Among them, 28 (53.85%) are male. The average age at presentation is 7.21 ± 4.15. Genome-wide RNA profiling were performed on fresh-frozen surgical samples. Tumor infiltrating immune cell percentages were inferred by the cibersort immune deconvolution algorithm.
RESULTS
A total of 13 leading genes, including DLL1, ASIC2, SLC22A17, TRPM3, RPS2P5 and KCNC3, were found to be significantly associated with overall survival (All P < 0.001). A risk score was constructed, which is indicative of overall survival (Hazard Ratio [HR] = 2.720, 95% confidence interval [CI] = 1.798 ~ 4.112, P < 0.001) and recurrence-free survival (HR = 1.645, CI = 1.337 ~ 2.025, P < 0.001). After adjustment of clinical factors, the score remained significantly associated with overall survival (HR = 2.781, CI = 1.762 ~ 4.390, P < 0.001) and recurrence-free survival (HR = 1.604, CI = 1.292 ~ 1.992, P < 0.001). The percentage of Natural Killer and T follicular helper (Tfh) cells were higher in patients with better overall survival (P = 0.046 and 0.001, respectively). Furthermore, the Tfh percentage is also positively associated with mutation burdens in the expressed exonic regions (P < 0.001).
CONCLUSION
Higher mutation burdens are correlated with higher levels of tumor infiltrating Tfh cells, which is indicative of better post-surgery prognosis.