TH and DCX mRNAs in peripheral blood and bone marrow predict outcome in metastatic neuroblastoma patients

Autores de IIS La Fe

• Yania Yañez Peralta

  Autor

• David Hervás Marín

  Autor

• Elena Grau García

  Autor

• Juan Silvestre Oltra Soler

  Autor

• Gabriela Alejandra Perez Cataldo

  Autor

• Sarai Palanca Suela

  Autor

• Adela Cañete Nieto

  Autor

• Victoria Castel Sánchez

  Autor

Participantes ajenos a IIS La Fe

• Bermúdez M
• Márquez C

Grupos

• Hepatología experimental y Trasplante hepático

• Investigación Clínica y Traslacional en Cáncer

• Investigación Traslacional en Genética

• Reumatología

Abstract

Purpose In metastatic neuroblastoma (NB) patients, accurate risk stratification and disease monitoring would reduce relapse probabilities. This study aims to evaluate the independent prognostic significance of detecting tyrosine hydroxylase (TH) and doublecortin (DCX) mRNAs by reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) in peripheral blood (PB) and bone marrow (BM) samples from metastatic NB patients. Procedures RT-qPCR was performed on PB and BM samples from metastatic NB patients at diagnosis, post-induction therapy and at the end of treatment for TH and DCX mRNAs detection. Results High levels of TH and DCX mRNAs when detected in PB and BM at diagnosis independently predicted worse outcome in a cohort of 162 metastatic NB. In the subgroup of high-risk metastatic NB, TH mRNA detected in PB remained as independent predictor of EFS and OS at diagnosis. After the induction therapy, high levels of TH mRNA in PB and DCX mRNA in BM independently predicted poor EFS and OS. Furthermore TH mRNA when detected in BM predicted worse EFS. TH mRNA in PB samples at the end of treatment is an independent predictor of worse outcome. Conclusion TH and DCX mRNAs levels in PB and BM assessed by RT-qPCR should be considered in new pre-treatment risk stratification strategies to reliable estimate outcome differences in metastatic NB patients. In those high-risk metastatic NB, TH and DCX mRNA quantification could be used for the assessment of response to treatment and for early detection of progressive disease or relapses.

Keywords

• Neuroblastoma; Minimal residual disease; Reverse transcriptase quantitative polymerase chain reaction (RT-qPCR); TH; DCX