CD133 and MYCN Amplification Induce Chemo-Resistance and Reduce Average Survival Time in Pediatric Neuroblastoma

Objectives: Neuroblastoma (NB) is the most common pediatric solid tumor derived from the sympathetic nervous system. MYCN gene exists in nearly half of the NB patient and its association with rapid disease progression and poor outcome is controversial. Cancer Stem Cells (CSCs) characterization in NB has been rarely studied. This study is to figure out whether the MYCN gene and CSCs are associated with chemotherapy resistance and survival time in the NB patients. Methods: Based on unequivocal pathological diagnosis, 50 NB patients are recruited. MYSN amplification is measured before any therapy. The CSCs are derived and their multi-potencies are tested by directed differentiation. Response to chemotherapy and average survival time of these patients are gathered and compared with following groups: CD133+, CD133-, MYCN ≥ 5, MYCN<5, CD133+ plus MYCN ≥ 5, CD133- plus MYCN<5. Results: CD133+ CSCs differentiate into neuron like cells; CD133+ patients have significant poorer response to chemotherapy comparing with the CD133- patients (P<0.01); CD133+ and MYCN ≥ 5 patients have significantly shorter average survival time than the CD133- and MYCN<5 patients (P<0.01). Conclusions: CD133+ CSCs produce chemo-resistance. CD133 and MYCN amplification can be used together as a prognostic value for predicting disease outcome.