鉴定小儿神经母细胞瘤预后的铁蛋白沉积相关基因特征。

IF 1.5 4区医学 Q4 ONCOLOGY

Translational cancer research Pub Date : 2024-07-31 Epub Date: 2024-07-26 DOI:10.21037/tcr-24-269

Xijin Lin, Kongfeng Shao, Zhuangbin Lin, Qiandong Liang, Xiaoyan Li, Haiyan Chen, Junxin Wu

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引用次数: 0

摘要

背景：铁蛋白沉积相关基因与神经母细胞瘤（NB）患者预后的相关性仍然未知。本研究旨在建立一个预后铁蛋白沉积相关基因模型，以预测小儿NB患者的预后价值：方法：从公共数据库下载NB的基因表达阵列和临床特征。方法：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蛋白沉积相关基因与药物反应之间的相关性。预后模型采用最小绝对收缩和选择算子（LASSO）Cox回归法构建，并在ICGC队列的NB患者中进行了验证。单样本基因组富集分析（ssGSEA）用于量化免疫细胞浸润相关性：结果：总体而言，从 247 个样本中发现了 70 个与铁沉积相关的差异表达基因（DEGs）。然后，在单变量考克斯回归分析中，13个与铁沉积相关的基因与OS相关。五个预后铁变态相关 DEGs（pFR-DEGs）（STEAP3、MAP1LC3A、ULK2、MTOR 和 TUBE1）被定义为 DEGs 和预后铁变态相关基因的交叉点，并被用于构建预后特征。分析了五个pFR-DEGs与药物反应的相关性，盒图显示MTOR基因表达量最高，表明MTOR的表达与NB疾病进展有关。接收者操作特征曲线（ROC）显示该模型具有中等预测能力。生存分析表明，高风险组的总生存期（OS）较差（P=2.087×10-06）。单变量和多变量分析表明，风险评分是一个重要的预后风险因素[P=0.003，危险比（HR）=1.933]。免疫细胞浸润相关性分析表明，高风险组与更多的免疫细胞有关：结论：本研究表明，低危和高危 NB 患者的铁蛋白沉积相关基因表达存在差异。结论：本研究表明，低危和高危 NB 患者的铁蛋白沉积相关基因表达存在差异，铁蛋白沉积相关特征可作为预后预测工具。此外，免疫浸润可能在不同风险组别的 NB 患者中发挥重要作用。

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Identification of a ferroptosis-related gene signature for the prognosis of pediatric neuroblastoma.

Background: 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.

Methods: 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.

Results: 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) (STEAP3, MAP1LC3A, ULK2, MTOR and TUBE1), 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 MTOR gene expression was highest, suggesting that MTOR 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^-06). 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.

Conclusions: 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.

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来源期刊

Translational cancer research ONCOLOGY-

CiteScore

2.10

自引率

0.00%

发文量

252

期刊介绍： Translational Cancer Research (Transl Cancer Res TCR; Print ISSN: 2218-676X; Online ISSN 2219-6803; http://tcr.amegroups.com/) is an Open Access, peer-reviewed journal, indexed in Science Citation Index Expanded (SCIE). TCR publishes laboratory studies of novel therapeutic interventions as well as clinical trials which evaluate new treatment paradigms for cancer; results of novel research investigations which bridge the laboratory and clinical settings including risk assessment, cellular and molecular characterization, prevention, detection, diagnosis and treatment of human cancers with the overall goal of improving the clinical care of cancer patients. The focus of TCR is original, peer-reviewed, science-based research that successfully advances clinical medicine toward the goal of improving patients'' quality of life. The editors and an international advisory group of scientists and clinician-scientists as well as other experts will hold TCR articles to the high-quality standards. We accept Original Articles as well as Review Articles, Editorials and Brief Articles.