title: Truncated neurokinin-1 receptor is an ubiquitous antitumor target in hepatoblastoma, and its expression is independent of tumor biology and stage.
abstract: The substance P (SP; also known asTAC1)/neurokinin-1 receptor (NK1R; also known asTACR1) complex is a critical part in the development of cancer. Therefore, NK1R antagonists, such as the clinical drug aprepitant, are currently under investigation as future anticancer agents. In a previous study, NK1R (TACR1) was identified as a potent anticancer target in hepatoblastoma (HB). However, little is known regarding the exact distribution of this target among HB subsets and whether it correlates with clinical features and prognosis. In the present study, mRNA was isolated from 47 children with HB, and reverse transcription-quantitative polymerase chain reaction was performed on the samples to analyze the expression of full-length-TACR1(fl-TACR1) and truncated-TACR1(tr-TACR1). These data were correlated with data obtained from 9 tumor-free controls, as well as with the presence of metastasis, PRETEXT, vascular invasion, histology, age of diagnosis, multifocality,CTNNB1mutation, gender and overall survival. Additionally, the present study investigated a recently described 16-gene signature characterizing HB known to correlate with prognosis. Compared with tumor-free liver tissue, tumorous tissue expressedTACR1significantly higher for the truncated version (P=0.0301), and by trend also for the full-length version. Accordingly, the expression of fl-TACR1correlated with the expression of the truncated version (P=0.0074). Furthermore, a low expression of fl-TACR1correlated with characteristics of the 16-gene signature known to predict prognosis (P=0.0222). However, there was no correlation between tr-TACR1and the tumor characteristics investigated, including outcome, although a clear trend was observed for some tumor characteristics. The current results reinforced the previously described findings that in HB, tr-TACR1is overexpressed compared with tumor-free liver tissue. Furthermore, to the best of our knowledge, the present study demonstrated for the first time that tr-TACR1is expressed ubiquitously among the different subsets of HB. Therefore, NK1R may serve as a potent anticancer target in a large variety of patients with HB, independent of tumor biology and clinical stage.
authors: Department of Pediatric Surgery, Dr von Hauner Children's Hospital, Ludwig Maximilian University of Munich, D-80337 Munich, Germany.
authors: Agnès
authors: A
authors: Garnier
authors: Department of General, Visceral, Transplantation, Vascular and Thoracic Surgery, Hospital of the Ludwig Maximilian University of Munich, D-80336 Munich, Germany.
authors: Matthias
authors: M
authors: Ilmer
authors: Department of Pediatric Surgery, Dr von Hauner Children's Hospital, Ludwig Maximilian University of Munich, D-80337 Munich, Germany.
authors: Kristina
authors: K
authors: Becker
authors: Department of Pediatric Surgery, Dr von Hauner Children's Hospital, Ludwig Maximilian University of Munich, D-80337 Munich, Germany.
authors: Beate
authors: B
authors: Häberle
authors: Department of Pediatric Surgery, Dr von Hauner Children's Hospital, Ludwig Maximilian University of Munich, D-80337 Munich, Germany.
authors: Dietrich
authors: D
authors: VON Schweinitz
authors: Department of Pediatric Surgery, Dr von Hauner Children's Hospital, Ludwig Maximilian University of Munich, D-80337 Munich, Germany.
authors: Roland
authors: R
authors: Kappler
authors: Department of Pediatric Surgery, Dr von Hauner Children's Hospital, Ludwig Maximilian University of Munich, D-80337 Munich, Germany.
authors: Michael
authors: M
authors: Berger
keywords: antitumor target; apoptosis; aprepitant; hepatoblastoma; neurokinin-1 receptor; substance P