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整合批量测序和单细胞测序揭示了与神经母细胞瘤预后和免疫浸润相关的二硫化物诱导细胞焦亡潜在指数。

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

作者信息

Zhu Aiguo, Li Xin, Wang Jian

机构信息

Tianjin Cancer Hospital Airport Hospital, National Clinical Research Center for Cancer, Tianjin, China.

Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, 300060, China.

出版信息

J Cancer Res Clin Oncol. 2023 Dec;149(18):16647-16658. doi: 10.1007/s00432-023-05392-9. Epub 2023 Sep 15.

DOI:10.1007/s00432-023-05392-9
PMID:37721569
Abstract

PURPOSE

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.

METHODS

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.

RESULTS

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.

CONCLUSION

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.

摘要

目的

神经母细胞瘤是一种具有挑战性的儿科肿瘤,需要改进治疗策略。本研究探讨了由细胞内二硫键积累诱导的一种细胞死亡形式——二硫键化坏死在神经母细胞瘤中的作用及其对预后和免疫浸润的影响。

方法

我们根据与二硫键化坏死相关的基因表达对神经母细胞瘤样本进行亚组分析,并构建了二硫键化坏死潜能指数(DPI)以量化神经母细胞瘤中的二硫键化坏死水平。探讨了DPI、预后、免疫浸润和药物敏感性之间的相关性。

结果

结合RNA测序和单细胞数据集,我们发现较高的二硫键化坏死潜能指数(DPI)与神经母细胞瘤患者较差的预后相关,表明增强的二硫键应激和细胞功能障碍的有害影响。此外,我们发现较高的DPI与肿瘤微环境中免疫浸润的减少相关,突出了高DPI神经母细胞瘤中的免疫抑制环境。高DPI神经母细胞瘤可能受益于雌激素途径相关药物氟维司群。

结论

总体而言,本研究强调了二硫键化坏死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途径。

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