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Abstract This study explores migrasomes' role in neuroblastoma, a common malignant tumor in children, and their potential impact on tumor formation. We analyzed neuroblastoma RNA-seq datasets from public databases, including GSE62564, GSE181559, target, and fwr144. Through data normalization and unsupervised classification using migrasome-specific molecular markers, Differentially Expressed Genes were identified, followed by functional enrichment analysis. Our novel migrasome-associated machine learning model, MigScore, was developed using ten algorithms and 101 combinations, validated on two single-cell datasets. This enabled immune infiltration assessment and drug compatibility prediction, highlighting the utility of MS275, a histone deacetylase inhibitor. Results showed a significant inverse relationship between MigScore and favorable clinical outcomes, elucidating the link between migrasome pathways and tumor immunogenicity. These findings suggest that migrasomes are crucial in neuroblastoma prognosis, leading to the possibility of personalized treatment strategies and improved outcomes.

BackgroundNeuroblastoma (NB), characterized by its marked heterogeneity, is the most common extracranial solid tumor in children. The status and functionality of mitochondria are crucial in regulating NB cell behavior. While the significance of mitochondria-related genes (MRGs) in NB is still missing in key knowledge.Materials and methodsThis study leverages consensus clustering and machine learning algorithms to construct and validate an MRGs-related signature in NB. Single-cell data analysis and experimental validation were employed to characterize the pivotal role of FEN1 within NB cells.ResultsMRGs facilitated the classification of NB patients into 2 distinct clusters with considerable differences. The constructed MRGs-related signature and its quantitative indicators, mtScore and mtRisk, effectively characterize the MRGs-related patient clusters. Notably, the MRGs-related signature outperformed MYCN in predicting NB patient prognosis and was adept at representing the tumor microenvironment (TME), tumor cell stemness, and sensitivity to the chemotherapeutic agents Cisplatin, Topotecan, and Irinotecan. FEN1, identified as the most contributory gene within the MRGs-related signature, was found to play a crucial role in the communication between NB cells and the TME, and in the developmental trajectory of NB cells. Experimental validations confirmed FEN1’s significant influence on NB cell proliferation, apoptosis, cell cycle, and invasiveness.ConclusionThe MRGs-related signature developed in this study offers a novel predictive tool for assessing NB patient prognosis, immune infiltration, stemness, and chemotherapeutic sensitivity. Our findings unveil the critical function of FEN1 in NB, suggesting its potential as a therapeutic target.

IntroductionNeuroblastoma (NB) is a common extracranial tumor in children and is highly heterogeneous. The factors influencing the prognosis of NB are not simple.MethodsTo investigate the effect of cell senescence on the prognosis of NB and tumor immune microenvironment, 498 samples of NB patients and 307 cellular senescence-related genes were used to construct a prediction signature.ResultsA signature based on six optimal candidate genes (TP53, IL-7, PDGFRA, S100B, DLL3, and TP63) was successfully constructed and proved to have good prognostic ability. Through verification, the signature had more advantages than the gene expression level alone in evaluating prognosis was found. Further T cell phenotype analysis displayed that exhausted phenotype PD-1 and senescence-related phenotype CD244 were highly expressed in CD8+ T cell in MYCN-amplified group with higher risk-score.ConclusionA signature constructed the six MYCN-amplified differential genes and aging-related genes can be used to predict the prognosis of NB better than using each high-risk gene individually and to evaluate immunosuppressed and aging tumor microenvironment.

Cancer is a major public health issue globally and is one of the leading causes of death. Although available treatments improve the survival rate of some cases, many advanced tumors are insensitive to these treatments. Cancer cell differentiation reverts the malignant phenotype to its original state and may even induce differentiation into cell types found in other tissues. Leveraging differentiation-inducing therapy in high-grade tumor masses offers a less aggressive strategy to curb tumor progression and heightens chemotherapy sensitivity. Differentiation-inducing therapy has been demonstrated to be effective in a variety of tumor cells. For example, differentiation therapy has become the first choice for acute promyelocytic leukemia, with the cure rate of more than 90%. Although an appealing concept, the mechanism and clinical drugs used in differentiation therapy are still in their nascent stage, warranting further investigation. In this review, we examine the current differentiation-inducing therapeutic approach and discuss the clinical applications as well as the underlying biological basis of differentiation-inducing agents.

Neuroblastoma is the most common pediatric extracranial solid tumor. The 5-year survival rate for high-risk neuroblastoma is less than 50%, despite multimodal treatment. Pyroptosis, an inflammatory type of programmed cell death, manifested pro-tumor and anti-tumor roles in the adult tumor. Thus, we aimed to elucidate the function of pyroptosis in neuroblastoma. We classified neuroblastoma patients into two clusters based on the pyroptosis gene expression. We found high pyroptosis neuroblastoma manifested favorable overall survival and more anti-tumor immune cell infiltration. Based on the results of a stepwise Cox regression analysis, we built a four-gene predictive model including NLRP3, CASP3, IL18, and GSDMB. The model showed excellent predictive performance in internal and external validation. Our findings highlight that high pyroptosis positively correlated with neuroblastoma outcomes and immune landscape, which may pave the way for further studies on inducing pyroptosis therapy in high-risk neuroblastoma treatment.

Background: Neuroblastoma (NB), the most common solid tumor in children, exhibits vastly different genomic abnormalities and clinical behaviors. While significant progress has been made on the research of relations between clinical manifestations and genetic abnormalities, it remains a major challenge to predict the prognosis of patients to facilitate personalized treatments.Materials and Methods: Six data sets of gene expression and related clinical data were downloaded from the Gene Expression Omnibus (GEO) database, ArrayExpress database, and Therapeutically Applicable Research to Generate Effective Treatments (TARGET) database. According to the presence or absence of MYCN amplification, patients were divided into two groups. Differentially expressed genes (DEGs) were identified between the two groups. Enrichment analyses of these DEGs were performed to dig further into the molecular mechanism of NB. Stepwise Cox regression analyses were used to establish a five-gene prognostic signature whose predictive performance was further evaluated by external validation. Multivariate Cox regression analyses were used to explore independent prognostic factors for NB. The relevance of immunity was evaluated by using algorithms, and a nomogram was constructed.Results: A five-gene signature comprising CPLX3, GDPD5, SPAG6, NXPH1, and AHI1 was established. The five-gene signature had good performance in predicting survival and was demonstrated to be superior to International Neuroblastoma Staging System (INSS) staging and the MYCN amplification status. Finally, a nomogram based on the five-gene signature was established, and its clinical efficacy was demonstrated.Conclusion: Collectively, our study developed a novel five-gene signature and successfully built a prognostic nomogram that accurately predicted survival in NB. The findings presented here could help to stratify patients into subgroups and determine the optimal individualized therapy.

Objective The aim of the present study was to analyze the prognostic factors in patients with hepatoblastoma (HB) in our single center and to evaluate periostin (POSTN) expression in HB and its association with clinicopathological variables. In addition, the underlying mechanism of how POSTN promotes HB progression was discussed.Methods POSTN expression was investigated in HB tumors by immunohistochemistry (IHC), immunofluorescence (IF) and Western blot (WB). The association among POSTN expression, clinicopathological features and overall survival (OS) was also evaluated. The migration and adhesion ability of HB cells were measured using chemotaxis and cell-matrix adhesion assays, respectively. Epithelial-mesenchymal transition (EMT)-associated markers and activation of the ERK pathway were detected by WB.Results HB patients had poor prognosis which displayed lymph node metastasis, vascular invasion, POSTN and vimentin expression. POSTN expression was also associated with lymph node metastasis. Furthermore, overexpressed POSTN promoted migration and the adhesive ability of HB cells in vitro. In addition, we demonstrated that POSTN activated the MAPK/ERK pathway, upregulated the expression of Snail and decreased the expression of OVOL2. Finally, POSTN promoted the expression of EMT-associated markers.Conclusions POSTN might modulate EMT via the ERK signaling pathway, thereby promoting cellular migration and invasion. Our study also suggests that POSTN may serve as a therapeutic biomarker in HB patients.

Summary: The emergence of all-inorganic halide perovskites has shown great potential in photovoltaic and optoelectronic devices. However, the photo-induced phase segregation in lead mixed-halide perovskites has severely limited their application. Herein, by real-time monitoring the photoluminescence (PL) spectra of metal mixed-halide perovskites under light irradiation, we found that the photo-induced phase transition can be significantly inhibited by B-site doping. For pristine mixed-halide perovskites, an intermediate phase of CsPbBrxI3-x can only be stabilized under low excitation power. After introducing Sn2+ ions, such intermediate phase can be stabilized in nitrogen atmosphere under high excitation power and phase segregation can be started after the exposure in oxygen due to oxidization of Sn2+. Replacing Sn2+ by Mn2+ can further improve the intermediate phase's tolerance to oxygen proving that B-site doping in perovskites structure by Sn2+ or Mn2+ could effectively minimize the light-induced phase segregation and promote them to serve as promising candidates in photovoltaic and light-emitting devices.

Purpose: Breast cancer has over the years been one of major acute carcinomas in women. This study investigated the fundamental mechanistic functions of the lncRNA-NEAT1/miR-148a-3p/Wnt/β-catenin axis in moderating cell viability, apoptosis and autophagy in Breast Cancer (BC). Methods: RT-qPCR measured expression of lncRNA NEAT1 and microRNA-148a-3p in human cell lines for Breast Cancer. Cell transfection upregulated or silenced the genes with CCK-8, western blot and FCM apoptosis assays determining the cellular growth, proliferation and protein expression related to autophagy biomarkers. Furthermore, luciferase assay analyzed the luciferase activity of lncRNANEAT1 and microRNA-148a-3p Results: The outcomes indicated that LncRNA-NEAT1 was upregulated in BC cell lines and promoted cell viability, autophagy and inhibited Apoptosis in BC cells. However, lncRNA-NEAT1 knockdown inhibited cell viability, autophagy and enhanced apoptosis. In addition, lncRNA-NEAT1 directly targeted microRNA-148a-3p. And, it was found that microRNA-148a-3p overturns the cellular viability, autophagy and inhibitory effects on Apoptosis imposed by lncRNA-NEAT1 overexpression. Lastly, overexpressed lncRNA-NEAT1 activated the Wnt/β-catenin regulatory network through sponging microRNA-148a-3p in BC cell lines. Conclusion The present study showcased that lncRNA-NEAT1 could enhance tumor development in breast cancer via playing the role of molecular sponge to microRNA-148a-3p, and eventually hyper invigorating the Wnt/β-catenin regulatory network. [ABSTRACT FROM AUTHOR]