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


METHODS
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.


CONCLUSIONS
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.
Unidad de Oncología Pediátrica, Hospital La Fe, Avda. Fernando Abril Martorell, 106, 46026, Valencia, Spain. yanyez_yan@gva.es.
Yania
Y
Yáñez
Unidad de Bioestadística, Hospital La Fe, Valencia, Spain.
David
D
Hervás
Unidad de Oncología Pediátrica, Hospital La Fe, Avda. Fernando Abril Martorell, 106, 46026, Valencia, Spain.
Elena
E
Grau
Unidad de Genética y Diagnóstico Prenatal, Hospital La Fe, Valencia, Spain.
Silvestre
S
Oltra
Laboratorio de Biología Molecular, Hospital La Fe, Valencia, Spain.
Gema
G
Pérez
Laboratorio de Biología Molecular, Hospital La Fe, Valencia, Spain.
Sarai
S
Palanca
Servicio de Oncología Pediátrica, Hospital Virgen de la Arrixaca, Murcia, Spain.
Mar
M
Bermúdez
Servicio de Oncología Pediátrica, Hospital Virgen del Rocio, Seville, Spain.
Catalina
C
Márquez
Unidad de Oncología Pediátrica, Hospital La Fe, Avda. Fernando Abril Martorell, 106, 46026, Valencia, Spain.
Adela
A
Cañete
Unidad de Oncología Pediátrica, Hospital La Fe, Avda. Fernando Abril Martorell, 106, 46026, Valencia, Spain.
Victoria
V
Castel
D000293:Adolescent; D000328:Adult; D014408:Biomarkers, Tumor / Q000097:blood / Q000235:genetics; D001853:Bone Marrow / Q000378:metabolism* / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008869:Microtubule-Associated Proteins / Q000097:blood / Q000235:genetics*; D009362:Neoplasm Metastasis; D009447:Neuroblastoma / Q000097:blood / Q000235:genetics* / Q000473:pathology*; D009479:Neuropeptides / Q000097:blood / Q000235:genetics*; D011379:Prognosis; D012333:RNA, Messenger / Q000097:blood / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000097:blood / Q000235:genetics*; D055815:Young Adult
D014408:Biomarkers, Tumor; C000714328:DCX protein, human; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides; D012333:RNA, Messenger; D014446:Tyrosine 3-Monooxygenase
DCX; Minimal residual disease; Neuroblastoma; Reverse transcriptase quantitative polymerase chain reaction (RT-qPCR); TH