Neuroblastoma (NB) is one of the most common solid tumors in children with varied clinical outcomes. Although there are some several risk stratification systems currently, their clinical applications are limited due to the testing conditions of different laboratory and the heavy financial burden on patients. TrkA is coded by NTRK1 , belonging to tropomyosin receptor kinase family. We have observed that TrkA was differentially expressed in paraffin tissue sections of NB. The aim of this study was to determine the immunohistochemical-score of TrkA as an independent prognostic factor for NB and establish a useful prognostic model for postoperative patients.
We systematically summarized the relationship between immunochemistry (IHC) score of TrkA and clinicopathological parameters in 86 NB cases. Fluorescence in situ hybridization (FISH) and qRT-PCR were used to detect NTRK1 gene fusion. Furthermore, GSE96631, GSE16476, GSE49710 and GSE73537 datasets, originated from Gene Expression Omnibus (GEO), were analyzed to figure out the NTRK1 related molecular characteristics by bioinformatics methods. And combined TrkA immunohistochemical-score with clinicopathologic parameters to construct a prognostic nomogram of overall survival (OS) for NB.
In clinical samples and GEO database analyses, patients in the NTRK1 / TrkA low expression group showed significantly poorer outcome than patients in high group. Multivariate cox regression analysis demonstrated NTRK1 / TrkA as an independent prognostic factor for NB survival. Neither Fluorescence in situ hybridization nor qRT-PCR detected evidence for NTRK1 gene fusion in clinical samples, indicating that differential expression in NTRK1 / TrkA are caused by epigenetic changes. Bioinformatics analyses revealed that MYC target related pathway may play a critical role in low expression of TrkA, leading to unfavorable prognoses of NB.
The results of this study suggest that the IHC score of TrkA may be used as an independent predictor of postoperative OS of patients with NB. By combining the IHC score of TrkA and clinicopathological features, the proposed nomogram provides a feasible predictive tool for postoperative patients with NB. Simultaneously, this study also reveals that Trk inhibitors are not supposed to be taken in NB patients.