Truncated Neurokinin-1 Receptor is an Ubiquitous Antitumor Target in Hepatoblastoma, and Its Expression is Independent of Tumor Biology and Stage

Overview

Journal Oncol Lett

Specialty Oncology

Date 2016 Feb 13

PMID 26870298

Citations 7

Authors

Agnes Garnier

Matthias Ilmer

Kristina Becker

Beate Haberle

Dietrich von Schweinitz

Roland Kappler

Michael Berger

Affiliations

Soon will be listed here.

Abstract

The substance P (SP; also known as )/neurokinin-1 receptor (NK1R; also known as ) 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 () 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- (fl-) and truncated- (tr-). 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, mutation, 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 expressed significantly higher for the truncated version (P=0.0301), and by trend also for the full-length version. Accordingly, the expression of fl- correlated with the expression of the truncated version (P=0.0074). Furthermore, a low expression of fl- correlated with characteristics of the 16-gene signature known to predict prognosis (P=0.0222). However, there was no correlation between tr- and 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- is overexpressed compared with tumor-free liver tissue. Furthermore, to the best of our knowledge, the present study demonstrated for the first time that tr- is 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.

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