Distinct Expression Profiles of Neuroblastoma-Associated mRNAs in Peripheral Blood and Bone Marrow of Non-High-Risk and High-Risk Neuroblastoma Patients
Naoko Nakatani,
Kaung Htet Nay Win,
Cho Yee Mon,
Tomoko Fujikawa,
Suguru Uemura,
Atsuro Saito,
Toshiaki Ishida,
Takeshi Mori,
Daiichiro Hasegawa,
Yoshiyuki Kosaka,
Shotaro Inoue,
Akihiro Nishimura,
Nanako Nino,
Akihiro Tamura,
Nobuyuki Yamamoto,
Kandai Nozu,
Noriyuki Nishimura
Affiliations
Naoko Nakatani
Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan
Kaung Htet Nay Win
Department of Public Health, Kobe University Graduate School of Health Science, Kobe 654-0142, Japan
Cho Yee Mon
Department of Public Health, Kobe University Graduate School of Health Science, Kobe 654-0142, Japan
Tomoko Fujikawa
Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan
Suguru Uemura
Department of Hematology/Oncology, Kobe Children’s Hospital, Kobe 650-0047, Japan
Atsuro Saito
Department of Hematology/Oncology, Kobe Children’s Hospital, Kobe 650-0047, Japan
Toshiaki Ishida
Department of Hematology/Oncology, Kobe Children’s Hospital, Kobe 650-0047, Japan
Takeshi Mori
Department of Hematology/Oncology, Kobe Children’s Hospital, Kobe 650-0047, Japan
Daiichiro Hasegawa
Department of Hematology/Oncology, Kobe Children’s Hospital, Kobe 650-0047, Japan
Yoshiyuki Kosaka
Department of Hematology/Oncology, Kobe Children’s Hospital, Kobe 650-0047, Japan
Shotaro Inoue
Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan
Akihiro Nishimura
Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan
Nanako Nino
Department of Hematology/Oncology, Kobe Children’s Hospital, Kobe 650-0047, Japan
Akihiro Tamura
Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan
Nobuyuki Yamamoto
Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan
Kandai Nozu
Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan
Noriyuki Nishimura
Department of Public Health, Kobe University Graduate School of Health Science, Kobe 654-0142, Japan
Non-high-risk (non-HR) neuroblastoma (NB) patients have excellent outcomes, with more than a 90% survival rate, whereas HR NB patients expect less than a 50% survival rate. Metastatic disease is the principal cause of death among both non-HR and HR NB patients. Previous studies have reported the significant but limited prognostic value of quantitative PCR (qPCR)-based assays, measuring overlapping but different sets of neuroblastoma-associated mRNAs (NB-mRNAs), to detect metastatic disease in both non-HR and HR patient samples. A droplet digital PCR (ddPCR)-based assay measuring seven NB-mRNAs (CRMP1, DBH, DDC, GAP43, ISL1, PHOX2B, and TH mRNAs) was recently developed and exhibited a better prognostic value for HR patient samples than qPCR-based assays. However, it remained to be tested on non-HR patient samples. In the present study, we employed the ddPCR-based assay to study peripheral blood (PB) and bone marrow (BM) samples collected at diagnosis from eight non-HR and eleven HR cases and characterized the expression profiles of NB-mRNAs. The most highly expressed NB-mRNAs in PB and BM differed between non-HR and HR cases, with the CRMP1 mRNA being predominant in non-HR cases and the GAP43 mRNA in HR cases. The levels of NB-mRNAs in PB and BM were 5 to 1000 times lower in non-HR cases than in HR cases. The PB to BM ratio of NB-mRNAs was 10 to 100 times higher in non-HR cases compared to HR cases. The present case series suggests that non-HR and HR NB patients have the distinct expression profiles of NB-mRNAs in their PB and BM.
