A nomogram for predicting recurrence-free survival of intermediate and high-risk neuroblastoma.

This study aimed to confirm the independent risk factors for recurrence-free survival (RFS) in intermediate and high-risk neuroblastoma (NB) patients and set up an effective nomogram model for predicting the recurrence of NB. A total of 212 children with intermediate- and high-risk neuroblastoma, who had ever achieved complete remission (CR) or very good partial remission (VGPR) after standardized treatment in this hospital, were chosen as study objects. After retrospective analysis of the clinical data, Cox regression model was used to explore the factors related to the recurrence of neuroblastoma, to determine the variables to construct the Nomogram. The consistency index would predict the accuracy of this nomogram. RFS rate in 1-year, 3-year, 5-year, and 10-year was 0.811, 0.662, 0.639, and 0.604, respectively. Children with MYCN amplification had a higher neuron-specific enolase (NSE) value (P = 0.031) at the initial diagnosis than MYCN non-amplification. The univariate analysis predicted that increased vanillylmandelic acid (VMA) and NSE value and dehydrogenase (LDH) > 1000 U/L were important adverse factors for the recurrence of NB. Multivariate analysis demonstrated that age at diagnosis, tumor localization, MYCN state, histologic subtype, and tumor capsule were significantly associated with RFS (all P values < 0.05). Nomograms were established for predicting the recurrence of NB according to the Cox regression analysis. Internal verification by the Bootstrap method showed that the prediction of the nomogram's consistency index (C-index) was 0.824 (P = 0.023).   Conclusion: Age at diagnosis, tumor localization, MYCN state, histologic category, and tumor capsule were independent risk factors for the recurrence of NB. The nomogram model could accurately predict the recurrence of children with neuroblastoma. What is Known: • The prognoses of neuroblastoma (NB) could vary greatly due to the high heterogeneity, the 5-year survival rate of low-risk NB exceeded 90%, while the 5-year survival rate of children in the intermediate and high-risk groups was not satisfactory.. What is New: • Increased vanillylmandelic acid (VMA) and neuron-specific enolase (NSE) value, and lactate dehydrogenase (LDH)>1000U/L were important adverse factors for the recurrence of NB. • NSE value was more valuable for predicting NB recurrence.

Exploring the prognosis of neuroblastoma in adolescents and adults: a case series and literature review.

Neuroblastoma (NB) is one of the most common extracranial malignant solid tumors in childhood, and over 90% of NBs are diagnosed in children under the age of 10 years old. For patients between 14 and 18 years old or older than 18 years, due to the rarity of NB, few studies have been performed in this population. Defined "adolescent cases" as individuals in 14-18 years old and "adult cases" as older than 18 years old, we reported five NB cases of adolescents and adults in our hospital. 137 cases presented a review of published literature on this topic. Clinicopathological factors and treatment modalities used of the 142 patients were assessed for their prognostic value. Better outcomes were found in adolescent patients rather than adult patients (p=0.012). Patients diagnosed with neuroblastoma or ganglioneuroblastoma (nodular type) (p=0.006) and with distant metastasis (p<0.001) were characterized by poor outcomes. Distant metastasis was an independent adverse influencing factor for overall survival in adolescent and adult NB patients. Regarding treatment modalities, complete surgical resection was a significant factor improving the survival for such patients (p<0.001). For patients with distant metastasis, a significantly longer progression-free survival with chemotherapy than without chemotherapy (p=0.038), whereas chemotherapy did not show an advantage on patients with localized disease (p=0.039). The prognosis of NB in adolescent and adult patients was worse than that in children. These two groups also showed heterogeneity in clinical factors, genetic factors, and treatment tolerance. The rarity of adolescent and adult NB can lead to misdiagnosis and incorrect management. Further optimization of chemotherapy regimens and dosage for adolescent and adult NB patients is needed. The anti-GD2 immunotherapy may be an effective approach for treatment.

BCL11A Facilitates Cell Proliferation and Metastasis in Neuroblastoma via Regulating the PI3K/Akt Signaling Pathway.

PURPOSE: The study aims to access the value of B-cell lymphoma/leukemia 11A (BCL11A) in the prognosis of patients with neuroblastoma (NB) and to explore its role and possible mechanism in NB. METHODS: Tumor specimens from 53 children with neuroblastoma were evaluated for the relationship between BCL11A expression level and prognosis of NB patients. Online datasets like SEQC and Asgharzadeh were analyzed to further check out the suppose.The role of BCL11A in the proliferation and migration of NB cells was studied by functional experiments such as CCK8, colony formation, flow cytometry, transwell and wound healing assay after knocking down BCL11A by small interfering RNA (siRNA) in vitro. The protein makers of the potential pathways were tested by western blot. RESULTS: High expression of BCL11A in NB patients was closely correlated with high-risk and poor prognosis. The proliferation and migration abilities of NB cell lines SK-N-BE(2) and IMR-32 were significantly impaired by silencing BCL11A. Downregulation of BCL11A expression level in NB cells inhibited the epithelial-mesenchymal transition (EMT) process and affected the PI3K/Akt signaling pathway. CONCLUSION: As a prognostic indicator of survival in NB patients, BCL11A might serve as a potential therapeutic target. BCL11A played a regulatory role in cell proliferation, invasion, and migration in NB, which may be through the PI3K/AKT signaling pathway and induce EMT.

Single-cell profiling of peripheral neuroblastic tumors identifies an aggressive transitional state that bridges an adrenergic-mesenchymal trajectory.

Peripheral neuroblastic tumors (PNTs) represent a spectrum of neural-crest-derived tumors, including neuroblastoma, ganglioneuroblastoma, and ganglioneuroma. Malignant cells in PNTs are theorized to interconvert between adrenergic/noradrenergic and mesenchymal/neural crest cell states. Here, single-cell RNA-sequencing analysis of 10 PNTs demonstrates extensive transcriptomic heterogeneity. Trajectory modeling suggests that malignant neuroblasts move between adrenergic and mesenchymal cell states via an intermediate state that we term "transitional." Transitional cells express programs linked to a sympathoadrenal development and aggressive tumor phenotypes such as rapid proliferation and tumor dissemination. Among primary bulk tumor patient cohorts, high expression of the transitional gene signature is predictive of poor prognosis compared with adrenergic and mesenchymal expression patterns. High transitional gene expression in neuroblastoma cell lines identifies a similar transitional H3K27-acetylation super-enhancer landscape. Collectively, our study supports the concept that PNTs have phenotypic plasticity and uncovers potential biomarkers and therapeutic targets.