Lin Xijin, Shao Kongfeng, Lin Zhuangbin, Liang Qiandong, Li Xiaoyan, Chen Haiyan, Wu Junxin
Department of Radiation Oncology, Fujian Children's Hospital (Fujian Branch of Shanghai Children's Medical Center), College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, China.
Department of Radiation Oncology, Fujian Medical University Union Hospital, Fuzhou, China.
Transl Cancer Res. 2024 Jul 31;13(7):3678-3694. doi: 10.21037/tcr-24-269. Epub 2024 Jul 26.
Ferroptosis-related genes are correlated with the prognosis of patients with neuroblastoma (NB) remains unknown. This study aims to establish a prognostic ferroptosis-related gene model for predicting prognostic value in pediatric NB patients.
The gene expression array and clinical characteristics of NB were downloaded from a public database. Correlations between ferroptosis-related genes and drug responses were analyzed by Childhood Cancer Therapeutics. The prognostic model was constructed by least absolute shrinkage and selection operator (LASSO) Cox regression and was validated in NB patients from the ICGC cohort. The survival analysis was performed by Cox regression analysis. single-sample gene set enrichment analysis (ssGSEA) was used to quantify the immune cell infiltration correlation.
Overall, 70 genes were identified as ferroptosis-related differentially expressed genes (DEGs) from 247 samples. Then, 13 ferroptosis-related genes were correlated with OS in the univariate Cox regression analysis. Five prognostic ferroptosis-related DEGs (pFR-DEGs) (, , , and ), which were defined as the intersection of DEGs and prognostic ferroptosis-related genes, were identified and utilized to construct the prognostic signature. The correlation between five pFR-DEGs and drug responses was analyzed, and the box plots indicated that gene expression was highest, suggesting that expression is related to progressive NB disease. The receiver operating characteristic (ROC) curve showed that the model had moderate predictive power. The survival analysis indicated that the high-risk group had poor overall survival (OS) (P=2.087×10). Univariate and multivariate analyses identified the risk score as a significant prognostic risk factor [P=0.003, hazard ratio (HR) =1.933]. Immune cell infiltration correlation analysis showed that the high-risk group was related to more immune cells.
The present study indicated a difference in ferroptosis-related gene expression between low- and high-risk NB patients. The ferroptosis-related signature could serve as a prognostic prediction tool. Additionally, immune infiltration might play an important role in different risk groups for NB patients.
铁死亡相关基因与神经母细胞瘤（NB）患者的预后是否相关尚不清楚。本研究旨在建立一个预后铁死亡相关基因模型，以预测儿童NB患者的预后价值。
从公共数据库下载NB的基因表达阵列和临床特征。通过儿童癌症治疗学分析铁死亡相关基因与药物反应之间的相关性。采用最小绝对收缩和选择算子（LASSO）Cox回归构建预后模型，并在ICGC队列的NB患者中进行验证。通过Cox回归分析进行生存分析。采用单样本基因集富集分析（ssGSEA）量化免疫细胞浸润相关性。
总体而言，从247个样本中鉴定出70个基因作为铁死亡相关差异表达基因（DEG）。然后，在单变量Cox回归分析中，13个铁死亡相关基因与总生存期（OS）相关。确定了五个预后铁死亡相关DEG（pFR-DEG）（ 、 、 、 和 ），它们被定义为DEG与预后铁死亡相关基因的交集，并用于构建预后特征。分析了五个pFR-DEG与药物反应之间的相关性，箱线图表明 基因表达最高，表明 表达与进展期NB疾病相关。受试者工作特征（ROC）曲线显示该模型具有中等预测能力。生存分析表明，高危组的总生存期（OS）较差（P=2.087×10）。单变量和多变量分析确定风险评分是一个显著的预后风险因素[P=0.003，危险比（HR）=1.933]。免疫细胞浸润相关性分析表明，高危组与更多免疫细胞相关。
本研究表明低危和高危NB患者在铁死亡相关基因表达上存在差异。铁死亡相关特征可作为一种预后预测工具。此外，免疫浸润可能在NB患者的不同风险组中起重要作用。
