Li Wanrong, Li Xin, Xia Yuren, Wang Jian
Tianjin Cancer Hospital Airport Hospital, 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, China.
Front Genet. 2022 May 19;13:809587. doi: 10.3389/fgene.2022.809587. eCollection 2022.
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.
神经母细胞瘤是最常见的小儿颅外实体瘤。尽管进行了多模式治疗，高危神经母细胞瘤的5年生存率仍低于50%。细胞焦亡是一种炎症性程序性细胞死亡，在成人肿瘤中表现出促肿瘤和抗肿瘤作用。因此，我们旨在阐明细胞焦亡在神经母细胞瘤中的作用。我们根据细胞焦亡基因表达将神经母细胞瘤患者分为两个亚群。我们发现高细胞焦亡神经母细胞瘤表现出良好的总生存率和更多的抗肿瘤免疫细胞浸润。基于逐步Cox回归分析结果，我们构建了一个包含NLRP3、CASP3、IL18和GSDMB的四基因预测模型。该模型在内部和外部验证中均表现出优异的预测性能。我们的研究结果表明，高细胞焦亡与神经母细胞瘤的预后和免疫格局呈正相关，这可能为高危神经母细胞瘤治疗中诱导细胞焦亡疗法的进一步研究铺平道路。
