Identification and analysis of endoplasmic reticulum stress-related genes in neuroblastoma and construction of a prognostic gene signature.

Neuroblastoma (NB) is one of the most common malignant tumors in children. Despite intensive multimodal treatments, patients with high-risk NB still have a poor prognosis; therefore, early identification of high-risk patients based on reliable NB biomarkers is essential. Endoplasmic reticulum (ER) stress has been demonstrated to play a vital role in cancer biology; however, it is unclear whether ER stress-related genes are involved in NB and should be further explored as new potential diagnostic and prognostic targets. We searched publicly available datasets with the aim to identify ER stress-related genes with a role in NB and establish a predictive model using ER stress-related signatures based on clinical information. Seventy-three ER stress-related genes were differentially expressed in NB cells; most of them were involved in biological processes such as intrinsic apoptotic signaling pathways and cellular responses to abiotic stimuli. Protein-protein interaction (PPI) analysis revealed hub genes, among which FN1 and MAPK8 were associated with the prognosis for patients with NB. A risk prediction model established based on 10 differentially expressed ER stress-related genes, including MAP2, PRKCD, MAPK8IP1, JPH1, TPP1, BCL2, EDN1, THBS1, MAPK8, and SERPINA3, could reliably identify patients with NB who had a high risk of poor prognosis. Among the 73 ER stress-related genes differentially expressed in NB, the 2 hub and 10 risk prediction-related genes could potentially serve as therapeutic biomarkers and prognostic indicators for patients with NB.