CD133 expression and MYCN amplification induce chemoresistance and reduce average survival time in pediatric neuroblastoma

Abstract

Objectives: Neuroblastoma (NB) is the most common pediatric solid tumor derived from the sympathetic nervous system. MYCN is amplified in nearly half of patients with NB, and its association with rapid disease progression and poor outcome is controversial. Characterization of cancer stem cells (CSCs) in NBs has been rarely studied. This study was performed to determine whether MYCN and CD133+ CSCs are associated with chemotherapy resistance and the survival time of patients with NB. Methods: Fifty patients with an unequivocal pathological diagnosis of NB were recruited. MYCN expression levels were measured before therapy. CSCs were derived and their multipotency tested by directed differentiation. The patients’ responses to chemotherapy and average survival time were compared among the groups as follows: CD133+, CD133−, MYCN amplification ≥5 times (i.e. MYCN≥5), MYCN<5, CD133+ plus MYCN≥5, and CD133− plus MYCN<5. Results: CD133+ CSCs differentiated into neuron-like cells. CD133+ patients had a significantly poorer response to chemotherapy than did CD133− patients. CD133+ plus MYCN≥5 patients had a significantly shorter average survival time than did CD133− plus MYCN<5 patients. Conclusions: CD133+ CSCs are chemoresistance. CD133 expression and MYCN amplification can be used together as a prognostic indicator of disease outcome.