Analysis of High-Risk Neuroblastoma Transcriptome Reveals Gene Co-Expression Signatures and Functional Features

SIMPLE SUMMARY: Neuroblastoma is a solid cancerous tumor that forms in the nerve cells of children, most commonly in the adrenal glands, which are located on top of both kidneys. This cancer is usually diagnosed after it has spread to other parts of the body in advanced stages of the disease. Consequently, treatment is often a very aggressive combination of chemotherapy and radiotherapy. Also, the survival rate of neuroblastoma is less than 40%, and this is partially explained by the fact that individuals bear genetic features that might limit the response to current treatments, which are the same for all diagnosed children. Therefore, it is necessary to discover a more efficient and less harmful therapy for cancer that can be suitable for all patients, regardless of their heterogeneity. Hence, we aimed to identify the genes whose expression is shared by multiple high-risk neuroblastoma patients, as well as their biological function. We found 104 genes common for 58 individuals that are involved in crucial cellular processes for neuroblastoma development. Our observations propose a list of genes and their biological functions that can be further investigated as possible therapeutic targets for this type of cancer, regardless of the patient’s genetic features. ABSTRACT: Neuroblastoma represents a neoplastic expansion of neural crest cells in the developing sympathetic nervous system and is childhood’s most common extracranial solid tumor. The heterogeneity of gene expression in different types of cancer is well-documented, and genetic features of neuroblastoma have been described by classification, development stage, malignancy, and progression of tumors. Here, we aim to analyze RNA sequencing datasets, publicly available in the GDC data portal, of neuroblastoma tumor samples from various patients and compare them with normal adrenal gland tissue from the GTEx data portal to elucidate the gene expression profile and regulation networks they share. Our results from the differential expression, weighted correlation network, and functional enrichment analyses that we performed with the count data from neuroblastoma and standard normal gland samples indicate that the analysis of transcriptome data from 58 patients diagnosed with high-risk neuroblastoma shares the expression pattern of 104 genes. More importantly, our analyses identify the co-expression relationship and the role of these genes in multiple biological processes and signaling pathways strongly associated with this disease phenotype. Our approach proposes a group of genes and their biological functions to be further investigated as essential molecules and possible therapeutic targets of neuroblastoma regardless of the etiology of individual tumors.