Meta-analysis of mRNA, microRNA expression and chromosome aberrations in phaeochromocytoma and neuroblastoma
P. Szabo1, M. Pinter2, D. Szabo1, A. Zsippai1, A. Patocs3, A. Falus1, K. Racz1 & P. Igaz1
Background: The pathogenesis of neural crest-derived tumours (phaeochromocytoma and neuroblastoma) is complex, and several studies applying functional genomics approaches have been performed in these tumours to date. However, the comparison of their genomic features has not been performed yet.
Objective: We have carried out an in silico meta-analysis of altogether 1784 neuroblastoma and 351 phaeochromocytoma samples to establish similarities and differences using analysis of mRNA and microRNA expression, chromosome aberrations and a novel bioinformatical analysis based on cooperative game theory.
Methods: Datasets obtained from Gene Expression Omnibus and Array Express have been subjected to a complex bioinformatics analysis using Gene Spring, Gene Set Enrichment Analysis, Ingenuity Pathway Analysis and own algorithms.
Results: Comparison of neuroblastoma and phaeochromocytoma with other tumours revealed the over expression of genes involved in development of noradrenergic cells. Among these, the significance of paired-like homeobox 2b (PHOX2B) in phaeochromocytoma has not been reported previously. The analysis of similar expression patterns in neuroblastoma and phaeochromocytoma revealed the same anti-apoptotic strategies in these tumours. Cancer regulation by stathmin turned out to be the major difference between phaeochromocytoma and neuroblastoma. Underexpression of genes involved in neuronal cell-cell interactions was observed in unfavourable neuroblastoma. By the comparison of hypoxia- and Ras-associated phaeochromocytoma, we have found that enhanced insulin like growth factor 1 signalling may be responsible for the activation of Src homology 2 domain containing transforming protein 1 (SHC1), the main co-factor of RET. Hypoxia induced factor 1α (HIF1α) and vascular endothelial growth factor signalling included the most prominent gene expression changes between von Hippel-Lindau and multiple endocrine neoplasia type 2A-associated phaeochromocytoma and we have supplemented these previously described pathways with several new members.
Conclusions: These pathways include previously undescribed pathomechanisms of neuroblastoma and phaeochromocytoma and associated gene products may serve as diagnostic markers and therapeutic targets.
Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.
Funding: This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.