PHOX2B expression in bone marrow and peripheral blood is associated with metastasis and prognosis in patients with neuroblastoma

Background Paired-like homeobox 2B (PHOX2B) is specifically expressed in the nervous system including neuroblastoma cells, but little is known about the clinical significance of the expression of PHOX2B in bone marrow (BM) and peripheral blood (PB) samples of newly diagnosed neuroblastoma patients. Methods The expression of PHOX2B in 276 paired BM and PB samples of neuroblastoma patients at diagnosis was tested by quantitative reverse transcriptase polymerase chain reaction (RT-PCR). Then the relationship between PHOX2B level and clinical characteristics including metastasis and prognosis was explored by receiver operating characteristic (ROC) analysis and Kaplan-Meier method. Results We identified the combined expression of PHOX2B in both BM and PB provided a high diagnostic accuracy for metastasis of neuroblastoma patients (AUC = 0.920) with the sensitivity and specificity of 86.7% and 92.9%, respectively. At last, 246 patients were enrolled for prognostic analysis. The median follow-up time was 22 months. Positive expressions of PHOX2B in BM and PB at diagnosis were associated with worse EFS and OS in neuroblastoma patients (P < 0.05). What's worse, 19.7% (31/157) and 6.4% (10/157) patients with positive expression of PHOX2B in BM and PB samples in low/intermediate-risk group also had shorter EFS and poor OS (P < 0.05). CONCLUSIONS The expressions of PHOX2B in BM and PB were high in patients with unfavorable clinical characteristics. PHOX2B could be an appropriate biomarker for predicting metastasis and prognosis in patients with neuroblastoma.