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Background: Tribbles Homolog 3 (TRIB3) is a member of the pseudokinase family of tribbles and acts as an adaptor protein to regulate different cellular processes. Upregulation of TRIB3 expression was shown either as a favorable or an adverse prognostic factor in various adult malignancies. However, TRIB3 expression has not been examined in pediatric cancers. Neuroblastoma is the most common malignant solid tumor of childhood, which affects mostly children under 5 years old. Risk stratification of patients defined by International Neuroblastoma Risk Group was used to determine prognosis and treatment of the disease. This study aimed to examine the relationship between TRIB3 protein expression levels and clinicopathological features and survival of patients. Methods: TRIB3 protein expression was analyzed using immunohistochemical staining on formalin-fixed paraffin-embedded tissue samples of neuroblastoma patients (n = 56). Survival analyses were performed with Kaplan-Meier method and log-rank tests. Association between TRIB3 expression and clinicopathological characteristics were analyzed with Spearman's correlation. Results: Of the patients, 32.1% were in the low-risk group, 21.4% in the medium-risk group, and 46.4% in the high-risk group. Survival analysis was performed in the entire neuroblastoma patient group and sub-risk groups of neuroblastoma patients. In the entire patient group, there was no significant difference in overall survival (P =.202) and event-free survival (P =.172) between TRIB3-positive and -negative patients. However, when survival analyses were performed in each risk group, TRIB3 expression was significantly associated with higher overall survival (P =.034) and event-free survival (P =.032) in low-risk group neuroblastoma patients. Nevertheless, no association was found between TRIB3 expression and overall survival (P =.799) and event-free survival (P =.448) in high-risk neuroblastoma patients. Furthermore, a significant correlation was identified between 1p36 loss-of-heterozygosity and TRIB3 expression (P =.030). However, TRIB3 expression did not correlate with other clinicopathological features. Conclusion: TRIB3 expression is a potential predictive biomarker for low-risk neuroblastoma patients. [ABSTRACT FROM AUTHOR]

BACKGROUND: Tribbles Homolog 3 (TRIB3) is a member of the pseudokinase family of tribbles and acts as an adaptor protein to regulate different cellular processes. Upregulation of TRIB3 expression was shown either as a favorable or an adverse prognostic factor in various adult malignancies. However, TRIB3 expression has not been examined in pediatric cancers. Neuroblastoma is the most common malignant solid tumor of childhood, which affects mostly children under 5 years old. Risk stratification of patients defined by International Neuroblastoma Risk Group was used to determine prognosis and treatment of the disease. This study aimed to examine the relationship between TRIB3 protein expression levels and clinicopathological features and survival of patients. METHODS: TRIB3 protein expression was analyzed using immunohistochemical staining on formalin-fixed paraffin-embedded tissue samples of neuroblastoma patients (n = 56). Survival analyses were performed with Kaplan-Meier method and log-rank tests. Association between TRIB3 expression and clinicopathological characteristics were analyzed with Spearman's correlation. RESULTS: Of the patients, 32.1% were in the low-risk group, 21.4% in the medium-risk group, and 46.4% in the high-risk group. Survival analysis was performed in the entire neuroblastoma patient group and sub-risk groups of neuroblastoma patients. In the entire patient group, there was no significant difference in overall survival (P = .202) and event-free survival (P = .172) between TRIB3-positive and -negative patients. However, when survival analyses were performed in each risk group, TRIB3 expression was significantly associated with higher overall survival (P = .034) and event-free survival (P = .032) in low-risk group neuroblastoma patients. Nevertheless, no association was found between TRIB3 expression and overall survival (P = .799) and event-free survival (P = .448) in high-risk neuroblastoma patients. Furthermore, a significant correlation was identified between 1p36 loss-of-heterozygosity and TRIB3 expression (P = .030). However, TRIB3 expression did not correlate with other clinicopathological features. CONCLUSION: TRIB3 expression is a potential predictive biomarker for low-risk neuroblastoma patients. [ABSTRACT FROM AUTHOR]

Objectives: Neuroblastoma is the most common extracranial solid tumor in childhood. YAP (Yes‐associated protein) is a highly expressed protein in NB. Nestin is an important marker of neuronal differentiation in NB. Orthodenticle homeobox (OTX) is a transcription factor and is overexpressed in blastoma‐derived tumors. The aim of this study was to examine the potential roles of YAP‐1, Nestin, and OTX‐2 proteins in prognosis and risk stratification in neuroblastoma Methods: Tumor sections of 56 patients with different NB risk groups were analyzed. YAP‐1, Nestin, and OTX‐2 protein expression levels were evaluated by immunohistochemical staining in NB patient tissue samples. Results: YAP‐1, Nestin, and OTX‐2 protein expression levels were evaluated together with the clinical findings of NB patients. YAP‐1 was expressed in 18% of all tissues, while Nestin was expressed in 20.4%. OTX‐2 protein expression was found in 41.1% of the NB patients. YAP‐1 was expressed in 26.9% of high‐risk and 11.5% of low‐risk patients. Nestin was expressed in 24.4% high‐risk and 33.3% low‐risk patients. OTX‐2 was expressed in 68.2% high‐risk and 60% low‐risk patients.YAP‐1 was shown to provide survival advantages among risk groups. Interpretation: The findings of this study support that YAP‐1 may be a potential prognostic biomarker for staging and risk‐group assignment of NB patients. YAP‐1 expression in neuroblastoma is associated with significantly poorer survival probabilities and should be considered as a potential therapeutic target. OTX‐2 is a promising predictive biomarker candidate, but its mechanisms need further investigation in neuroblastoma, as nestin expression is not significantly linked to patient survival. [ABSTRACT FROM AUTHOR]

• Genetic variations in low-risk and high-risk NB patients were examined by WES. • The genetic variations found and compared with previous NB whole-exome sequencing studies in the cBioportal database. • Variants in ARID1A and NCOR2 , related to chromatin remodeling, were commonly mutated in cBioportal and high-risk patients. • Candidate gene variations associated with chromatin remodeling, RAS pathway, cell proliferation, and DNA repair mechanism. This study aimed to investigate the genetic aberrations in neuroblastoma (NB) by comparing high and low-risk NB patients by whole-exome sequencing (WES) and to reveal the heterogeneity and association between somatic variants and clinical features. Seven NB patients with available clinical data were included in the study (4 in the low-risk group and 3 in the high-risk group). WES was performed and somatic variants associated with NB genes in the COSMIC database were selected through bioinformatics pipeline analysis. Variants were determined using the Integrative Genomics Viewer (IGV). Some gene variations were found in both groups, including variations in oncogene and tumor suppressor genes. In general, candidate gene variations were associated with chromatin remodeling complexes, the RAS pathway, cell proliferation, and DNA repair mechanism. Some variations in CSF1R, MSH6, PTPN11, SOX9, RET, TSC1 , and DNMT1 genes were detected only in high-risk patients, while EP300, TET2, MYCN, PRDM1 , and ARID2 gene variations were detected only in low-risk patients. When high-risk gene variants were compared with the cBioportal cancer genomic database, two common gene variants (ARID1A and NCOR2) were identified. However, when low-risk gene variants were compared with the cBioportal cancer genomic database, no common genes were found. GO/KEGG enrichment analysis was performed to find relevant biological processes and molecular pathways related to gene variants, which will help to decipher the molecular mechanisms of NB tumorigenesis and the phenotypic differences between high-risk and low-risk patients. [ABSTRACT FROM AUTHOR]