Abstract
BackgroundThe prognostic value of immune-related genes and lncRNAs in neuroblastoma has not been elucidated, especially in subgroups with different outcomes. This study aimed to explore immune-related prognostic signatures.Materials and MethodsImmune-related prognostic genes and lncRNAs were identified by univariate Cox regression analysis in the training set. The top 20 C-index genes and 17 immune-related lncRNAs were included in prognostic model construction, and random forest and the Least Absolute Shrinkage and Selection Operator (LASSO) regression algorithms were employed to select features. The risk score model was constructed and assessed using the Kaplan-Meier plot and the receiver operating characteristic curve. Functional enrichment analysis of the immune-related lncRNAs was conducted using the STRING database.ResultsIn GSE49710, five immune genes (CDK4, PIK3R1, THRA, MAP2K2, and ULBP2) were included in the risk score five genes (RS5_G) signature, and eleven immune-related lncRNAs (LINC00260, FAM13A1OS, AGPAT4-IT1, DUBR, MIAT, TSC22D1-AS1, DANCR, MIR137HG, ERC2-IT1, LINC01184, LINC00667) were brought into risk score LncRNAs (RS_Lnc) signature. Patients were divided into high/low-risk score groups by the median. Overall survival and event/progression-free survival time were shortened in patients with high scores, both in training and validation cohorts. The same results were found in subgroups. In grouping ability assessment, the area under the curves (AUCs) in distinguishing different groups ranged from 0.737 to 0.94, better in discriminating MYCN status and high risk in training cohort (higher than 0.9). Multivariate Cox analysis demonstrated that RS5_G and RS_Lnc were the independent risk factors for overall and event/progression-free survival (all p-values <0.001). Correlation analysis showed that RS5_G and RS_Lnc were negatively associated with aDC, CD8+ T cells, but positively correlated with Th2 cells. Functional enrichment analyzes demonstrated that immune-related lncRNAs are mainly enriched in cancer-related pathways and immune-related pathways.ConclusionWe identified the immune-related prognostic signature RS5_G and RS_Lnc. The predicting and grouping ability is close to being even better than those reported in other studies, especially in subgroups. This study provided prognostic signatures that may help clinicians to choose optimal treatment strategies and showed a new insight for NB treatment. These results need further biological experiments and clinical validation.
Highlights
Neuroblastoma (NB), one of the most common malignant solid tumors in children, accounts for nearly 15% of childhood cancerrelated deaths [1, 2]
681 immune-related prognostic genes associated with overall survival (OS) time were identified, and a p-value
Neuroblastoma (NB) is a malignant solid tumor in children, which is linked with highly heterogeneous outcomes ranging from spontaneous regression without treatment to rapid progression after intensive multidisciplinary therapy [3, 29]
Summary
Neuroblastoma (NB), one of the most common malignant solid tumors in children, accounts for nearly 15% of childhood cancerrelated deaths [1, 2]. Over the past two decades, the International Neuroblastoma Risk Group (INRG) classification system has defined a unified approach for pretreatment assessment, which includes age at diagnosis, histology, the grade of tumor differentiation, MYCN status, 11q aberration, and ploidy [3]. According to the classification criteria, low- and intermediate-risk patients can receive reduced chemotherapy and attain good outcomes. The prognosis for high-risk patients is still dismal, even though they have received intensive chemotherapy, surgery, radiotherapy, and other combined therapies, and the long-term survival of these patients remains less than 50% [4,5,6]. The clinical use of these markers may be limited in some patients despite the elaborate risk stratification. The prognostic value of immune-related genes and lncRNAs in neuroblastoma has not been elucidated, especially in subgroups with different outcomes.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
