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.

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 neuroblastomaMethods: 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.

Nöroblastom, gelişmekte olan sinir sisteminden köken alan ve çocukluk çağının en sık görülen solid tümörüdür. Klinik seyri lokalize veya spontane gerileme gösterebilen hastalıktan, yoğun ve multimodal tedavi rejimlerine dirençli metastatik hastalığa değişen heterojen bir davranış göstermektedir. Ras Homolog Ailesi Üyesi B (RhoB), Rho GTPaz ailesinin bir üyesidir ve sitoiskeletet organizasyonunda, reseptör ve sinyal proteinlerinin iletiminde, DNA hasar tamirinde ve apoptozda rol oynar. RhoB ekspresyonu farklı erişkin kanser türlerinde incelenmiş ve farklı kanser türlerinde iyi veya kötü prognozla ilişkili olduğu saptanmıştır. Ne var ki, RhoB ekspresyonu aday bir prognostik biyobelirteç olarak pediatrik kanserlerde daha önce çalışılmamıştır. Yapılan çalışmamızda, RhoB protein ekspresyonu nöroblastom hastalarında immün histokimyasal boyama yöntemiyle incelenmiştir. RhoB ekspresyonu ile düşük, orta ve yüksek risk gruplarındaki nöroblastom hastalarının genel sağ kalımı ve olaysız sağ kalımları karşılaştırılmış ve RhoB ekspresyonu ile hastaların klinikopatolojik özellikleri Spearman’s korelasyon analizi ile incelenmiştir. Her ne kadar çalışmamızdaki hasta örneklem sayısı az olsa da çalışmamızda RhoB ekspresyonunun NB hastaları için iyi prognostik bir biyobelirteç olabileceği ortaya konmuştur.

Background: SMAC mimetics (SM) are compounds that are developed on secondary mitochondria-derived activators of caspase (SMAC) protein structure and sensitize cancer cells to cell death, either alone or in the presence of death ligands or chemotherapies. However, their efficacy as a single agent or in combination with chemotherapy is highly variable and limited. In this study, we aimed to identify the transcriptomic changes in the SH-SY5Y cells upon induction with SM using RNA sequencing (RNA-seq). Hence, the total gene expression changes to understand the mechanism of action of SM in SH-SY5Y cells were examined. Methods and Results: RNA sequencing was performed on LCL-161 (a monovalent type of SM) treated SH-SY5Y neuroblastoma cells. The significantly upregulated and downregulated genes were studied using Real-time PCR (Q-PCR). In addition to the intrinsic apoptotic pathways, we identified significant upregulation in the endoplasmic reticulum (ER)-stress-related genes upon LCL-161 induction in RNA-seq results. Conclusion: These results demonstrated that ER stress response pathways might play a role in the SM response in addition to previously known apoptotic or necroptotic pathways. Further studies are required to establish whether ER stress pathways act as pro-survival or pro-apoptotic pathways in this response.