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铁死亡特征预测鼻咽癌的预后和免疫微环境

英文原题:The ferroptosis signature predicts the prognosis and immune microenvironment of nasopharyngeal carcinoma.

查看英文原题

The ferroptosis signature predicts the prognosis and immune microenvironment of nasopharyngeal carcinoma.

PubMed 2023/02/02(内容时间) Sci Rep Q1 · IF 4.9(JCR 2025)

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中文摘要

鼻咽癌(NPC)是一种转移率高、预后差的癌症。越来越多的研究表明,铁死亡参与肿瘤的发展。同时,铁死亡相关基因(FRGs)与NPC预后之间的联系仍不清楚。

在本研究中,我们探索了NPC正常对照与肿瘤样本之间失调的FRGs。首先,与正常组织相比,在NPC组织中鉴定出36个差异表达的FRGs中有14个,其中ABCC1、GLS2、CS和HMGCR与患者不良预后相关。这四个铁死亡基因被用于共识聚类分析,两个风险相关FRGs(ABCC1和GLS2)被用于风险模型。ROC曲线显示该风险特征具有良好的预测性能。多因素分析显示,风险评分和瘤内TILs是与预后相关的独立危险因素。

此外,我们的结果表明该风险特征与免疫微环境相关。而且,高风险NPC患者对化疗药物敏感,包括axitinib、docetaxel、embelin、epothilone.B、parthenolide、thapsigargin、tipifarnib、vinorelbine。

最后,使用免疫组织化学在NPC组织中验证了ABCC1和GLS2的表达。总之,这些结果揭示了铁死亡可能是NPC的潜在生物标志物,代表了NPC治疗中预后和治疗策略的一个有前景的未来方向。

展开英文摘要原文

Nasopharyngeal carcinoma (NPC) is a cancer with a high metastatic rate and poor prognosis. Growing studies suggest that ferroptosis take part in the development of tumours. At the same time, the connection between ferroptosis-related genes (FRGs) and the prognosis of NPC remains unclear. In this study, we explored the dysregulated FRGs between normal control and tumour samples of NPC.

Firstly, 14 of 36 differentially expressed FRGs were identified in NPC tissues compared to normal tissues, among which ABCC1, GLS2, CS and HMGCR were associated with poor prognosis for patients. The four ferroptosis genes were used for consensus cluster analysis and two risk-related FRGs (ABCC1 and GLS2) were used in a risk model. The ROC curve revealed the good predictive performance of this risk signature. Multivariate analysis revealed that risk score and intratumoral TILs were independent risk factors linked to prognosis.

Additionally, our results suggested that the risk signature was attached to the immune microenvironment.

Moreover, the NPC patients with high risk were sensitive to chemotherapeutic drugs including axitinib, docetaxel, embelin, epothilone. B, parthenolide, thapsigargin, tipifarnib, vinorelbine.

Finally, the expression of ABCC1 and GLS2 was validated in NPC tissues using immunohistochemistry.

Together, these results revealed ferroptosis may be a potential biomarker in NPC and representing a promising future direction in prognosis and therapeutic strategy for the treatment of NPC.

论文信息

作者
Zhou J、Guo T、Zhou L、Bao M、Wang L、Zhou W、Tan S、Li G
第一作者单位
Academician Workstation, Changsha Medical University, Changsha, China. zhoujily0303@163.com.China
通讯作者单位
Academician Workstation, Changsha Medical University, Changsha, China. plws3298@163.com.China
文献类型
非美国政府资助研究
期刊
Scientific reports2023 Feb 2
原文标识
PubMed 36732567 · DOI 10.1038/s41598-023-28897-2