Since the development of high-throughput techniques, many studies have focused on defining gene expression-based prognostic signatures in neuroblastoma. The majority of these studies have defined signatures that identify differentially expressed genes between the currently defined clinical subgroups of neuroblastoma, such as high-risk vs. low-risk, alive vs. deceased, MYCN-amplified vs. non-amplified etc. Although these signatures do indeed provide important prognostic information to the current neuroblastoma stratification schemes, they are often closely associated with the pre-defined clinical subgroups. In this study, we use gene expression arrays from 3 independent cohorts consisting of over 800 tumors to identify gene expression patterns associated with early-death events amongst patients who succumb to the disease.
Gene Set Enrichment analyses on differentially expressed genes between early-death vs. late-death patients (death within or after 1 year from diagnosis, respectively) identified immunological processes amongst the main differences between the groups. Making use of previously defined immune cell-specific markers, we further examined expression patterns amongst high-risk neuroblastomas. Firstly, we find that expression of immune cell markers successfully separates high-risk patients into distinct subgroups. Interestingly, patients who succumb to the disease within 1 year from diagnosis displayed a significantly lower expression of markers associated with adaptive immune cells (specifically cytotoxic and helper T-cells). Furthermore, MYCN-amplified patients could be divided into two subgroups: one associated with low expression of adaptive immune makers and high expression of innate immune markers, and the second associated with a general lack of both adaptive and innate immunity markers. In this case, the latter group with a general lack of immune-cell markers was associated with early-death events.
Here we describe a subgroup of high-risk neuroblastoma patients who succumb to the disease within 1 year from diagnosis. This subgroup is characterized by a lack of adaptive immune-cell markers, suggesting immune-repression in these patients. Further investigation into potential underlying immodeficiencies or tumor-dependent immunosuppression in these patients will deepen our understanding of the aggressive factors associated with high-risk neuroblastoma patients.