研究动态
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融合bulk-seq和single-cell-seq技术揭示出与神经母细胞瘤预后和免疫浸润相关的巯基氧化物潜在指数。

Integrating bulk-seq and single-cell-seq reveals disulfidptosis potential index associating with neuroblastoma prognosis and immune infiltration.

发表日期:2023 Sep 15
作者: Aiguo Zhu, Xin Li, Jian Wang
来源: Cell Death & Disease

摘要:

神经母细胞瘤是一种具有改善治疗策略需求的具有挑战性的儿科肿瘤。本研究探讨了强烈细胞内二硫化物蓄积引起的一种细胞死亡形式——二硫化物死亡,以及其在神经母细胞瘤中的作用,对预后和免疫浸润的意义进行了研究。我们根据与二硫化物死亡相关的基因表达对神经母细胞瘤样本进行了分组,并构建了二硫化物死亡潜力指数(DPI)以量化神经母细胞瘤中的二硫化物死亡水平。我们探讨了DPI、预后、免疫浸润和药物敏感性之间的相关性。通过RNA测序和单细胞数据集的组合,我们发现高二硫化物死亡潜力指数(DPI)与神经母细胞瘤患者的较差预后相关,表明增强的二硫化物应激和细胞功能障碍的不利影响。此外,我们发现较高的DPI与肿瘤微环境中减少的免疫浸润相关,强调了高DPI神经母细胞瘤中存在的免疫抑制环境。DPI高的神经母细胞瘤可能受益于与雌激素途径相关的药物富全雌酮。总体而言,本研究突出了二硫化物死亡作为潜在治疗靶点的重要性,并强调了整合免疫调节策略的重要性,为改善神经母细胞瘤的管理提供了新的途径。 © 2023. 作者(们)已独家授权给施普林格-弗拉格德有限公司,隶属于施普林格自然出版集团。
Neuroblastoma is a challenging pediatric tumor with a need for improved treatment strategies. This study explores the role of disulfidptosis, a form of cell death induced by intracellular disulfide accumulation, in neuroblastoma and its implications for prognosis and immune infiltration.We subgrouped neuroblastoma samples based on disulfidptosis-related gene expression and constructed a disulfidptosis potential index (DPI) to quantify disulfidptosis levels in neurobalstoma. The correlation between DPI, outcome, immune infiltration, and drug sensitivity were explored.Combing RNA-seq and single-cell dataset, we found that higher disulfidptosis potential index (DPI) is associated with poorer outcomes in neuroblastoma patients, indicating the detrimental impact of enhanced disulfide stress and cellular dysfunction. Furthermore, we found that higher DPI is correlated with reduced immune infiltration within the tumor microenvironment, highlighting an immunosuppressive milieu in high DPI neuroblastomas. The DPI-high neuroblastoma may benefit from the estrogen pathway related drug fulvestrant.Overall, this study highlights the significance of disulfidptosis as a potential therapeutic target and underscores the importance of integrating immune modulation strategies, offering new avenues for improved management of neuroblastoma.© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.