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

  • Original Article – Cancer Research
  • Published:
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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.

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Acknowledgments

We thank Désirée Ramal for her help in the data management and all the Spanish collaborating hospitals who register their patients.

Funding

This work was supported in part by: FIS PS09/02323, FIS PS02/0315, Cancercare Foundation and APU Foundation.

Author information

Authors and Affiliations

  1. Unidad de Oncología Pediátrica, Hospital La Fe, Avda. Fernando Abril Martorell, 106, 46026, Valencia, Spain

    Yania Yáñez, Elena Grau, Adela Cañete & Victoria Castel

  2. Unidad de Bioestadística, Hospital La Fe, Valencia, Spain

    David Hervás

  3. Unidad de Genética y Diagnóstico Prenatal, Hospital La Fe, Valencia, Spain

    Silvestre Oltra

  4. Laboratorio de Biología Molecular, Hospital La Fe, Valencia, Spain

    Gema Pérez & Sarai Palanca

  5. Servicio de Oncología Pediátrica, Hospital Virgen de la Arrixaca, Murcia, Spain

    Mar Bermúdez

  6. Servicio de Oncología Pediátrica, Hospital Virgen del Rocio, Seville, Spain

    Catalina Márquez

Authors
  1. Yania Yáñez
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  2. David Hervás
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  3. Elena Grau
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  4. Silvestre Oltra
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  5. Gema Pérez
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  6. Sarai Palanca
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  7. Mar Bermúdez
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  8. Catalina Márquez
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  9. Adela Cañete
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  10. Victoria Castel
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Corresponding author

Correspondence to Yania Yáñez.

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Conflict of interest

The authors indicated no potential conflicts of interest.

Ethical approval

The study was approved by the Hospital La Fe Ethical Committee and was performed in accordance with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

All parents or guardians signed an informed consent statement for sample and data management from all patients included in the study.

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Yáñez, Y., Hervás, D., Grau, E. et al. TH and DCX mRNAs in peripheral blood and bone marrow predict outcome in metastatic neuroblastoma patients. J Cancer Res Clin Oncol 142, 573–580 (2016). https://doi.org/10.1007/s00432-015-2054-7

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  • DOI: https://doi.org/10.1007/s00432-015-2054-7

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