Yania Yáñez1, David Hervás2, Elena Grau3, Silvestre Oltra4, Gema Pérez5, Sarai Palanca5, Mar Bermúdez6, Catalina Márquez7, Adela Cañete3, Victoria Castel3. 1. Unidad de Oncología Pediátrica, Hospital La Fe, Avda. Fernando Abril Martorell, 106, 46026, Valencia, Spain. yanyez_yan@gva.es. 2. Unidad de Bioestadística, Hospital La Fe, Valencia, Spain. 3. Unidad de Oncología Pediátrica, Hospital La Fe, Avda. Fernando Abril Martorell, 106, 46026, Valencia, Spain. 4. Unidad de Genética y Diagnóstico Prenatal, Hospital La Fe, Valencia, Spain. 5. Laboratorio de Biología Molecular, Hospital La Fe, Valencia, Spain. 6. Servicio de Oncología Pediátrica, Hospital Virgen de la Arrixaca, Murcia, Spain. 7. Servicio de Oncología Pediátrica, Hospital Virgen del Rocio, Seville, Spain.
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.
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.
Authors: H Shimada; I M Ambros; L P Dehner; J Hata; V V Joshi; B Roald; D O Stram; R B Gerbing; J N Lukens; K K Matthay; R P Castleberry Journal: Cancer Date: 1999-07-15 Impact factor: 6.860
Authors: Rosa Noguera; Adela Cañete; Antonio Pellín; Amparo Ruiz; María Tasso; Samuel Navarro; Victoria Castel; Antonio Llombart-Bosch Journal: Cancer Genet Cytogenet Date: 2003-01-15
Authors: I M Ambros; J Benard; M Boavida; N Bown; H Caron; V Combaret; J Couturier; C Darnfors; O Delattre; J Freeman-Edward; C Gambini; N Gross; C M Hattinger; A Luegmayr; J Lunec; T Martinsson; K Mazzocco; S Navarro; R Noguera; S O'Neill; U Potschger; S Rumpler; F Speleman; G P Tonini; A Valent; N Van Roy; G Amann; B De Bernardi; P Kogner; R Ladenstein; J Michon; A D J Pearson; P F Ambros Journal: J Clin Oncol Date: 2003-06-01 Impact factor: 44.544
Authors: Janine Stutterheim; Annemieke Gerritsen; Lily Zappeij-Kannegieter; Ilona Kleijn; Rob Dee; Lotty Hooft; Max M van Noesel; Marc Bierings; Frank Berthold; Rogier Versteeg; Huib N Caron; C Ellen van der Schoot; Godelieve A M Tytgat Journal: J Clin Oncol Date: 2008-10-06 Impact factor: 44.544
Authors: Shahab Asgharzadeh; Araz Marachelian; Judith G Villablanca; Wei Yao Liu; Rebekah Kennedy; Richard Sposto; Arlene Naranjo; Sheena Tenney; Alice L Yu; M Fevzi Ozkaynak; Paul M Sondel; Julie R Park; Robert C Seeger Journal: Pediatr Blood Cancer Date: 2022-04-20 Impact factor: 3.838
Authors: Izhar S Batth; Long Dao; Arun Satelli; Abhisek Mitra; Sofia Yi; Hyangsoon Noh; Heming Li; Zachary Brownlee; Shouhao Zhou; Jeffrey Bond; Jing Wang; Jonathan Gill; Giselle S Sholler; Shulin Li Journal: Int J Cancer Date: 2020-06-23 Impact factor: 7.316
Authors: Na Hee Lee; Meong Hi Son; Young Bae Choi; Eunsang Yi; Ji Won Lee; Keon Hee Yoo; Ki Woong Sung; Hong Hoe Koo Journal: Cancer Res Treat Date: 2016-03-24 Impact factor: 4.679
Authors: Ruben Van Paemel; Roos Vlug; Katleen De Preter; Nadine Van Roy; Frank Speleman; Leen Willems; Tim Lammens; Geneviève Laureys; Gudrun Schleiermacher; Godelieve A M Tytgat; Kathy Astrahantseff; Hedwig Deubzer; Bram De Wilde Journal: Eur J Pediatr Date: 2020-01-03 Impact factor: 3.183