The crosstalk effect of cancer stem cells in the progression of pediatric medulloblastoma through signaling expression of CD133, CD44, and OCT4 with and without Wnt-b-catenin activation.

Abstract

Introduction: Cancer stem cells (CSCs) are principal drivers in medulloblastoma (MB) initiation, growth, and progression. Our study aimed to explore the expression of CD133, CD44, and OCT4 signaling markers and their effects on the progression of MB.

Material and methods: A retrospective cohort analysis was conducted on brain tissue of 24 pediatric cases of MB from 2016-2020. Protein expression levels of CSC markers CD133, CD44, and OCT4 were evaluated immunohistochemically and their correlation with b-catenin activity was statistically analyzed.

Results: The mean age of patients was 10.2 years (range 3-17), with 18 (75%) males and 6 (25%) females. b-catenin was expressed in 20 (83.3%) tumors, and 4 (16.7%) tumors showed no expression. CD133 was minimally expressed in 6 (25%) tumors and 18 tumors (75%) showed no expression. CD44 was highly expressed in 6 (25%) tumors and 18 (75%) tumors showed minimal to no expression. OCT4 was expressed in all tumors. Despite MBs with positive b-catenin expression and absent CD133 expression having longer progression-free survival (PFS), this impact on PFS did not reach statistical significance ( p = 0.76). However, statistically significant differences in PFS were observed in MBs with positively expressed b-catenin and minimal or no CD44 expression, which showed prolonged PFS ( p = 0.0064). MB patients who did not express CD133 and received combined radiotherapy (RTx) and chemotherapy (CTx) showed longer PFS compared to MB patients with minimal CD133 expression. However, this association was statistically insignificant ( p = 0.42). The impact of CD44 expression and chemoradiation on PFS was statistically significant ( p = 0.0035). MB patients with absent or minimal CD44 expression who received RTx and CTx showed the longest PFS.

Conclusions: Medulloblastomas not expressing CSC markers (CD133, CD44) are associated with prolonged PFS and less resistance to chemoradiation. However, b-catenin is considered the main predictor for prognosis when compared to CSC markers.