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铁死亡特征可预测鼻咽癌的预后和免疫微环境。

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

机构信息

Academician Workstation, Changsha Medical University, Changsha, China.

Department of Pathology, The Second Xiangya Hospital of Central South University, Changsha, China.

出版信息

Sci Rep. 2023 Feb 2;13(1):1861. doi: 10.1038/s41598-023-28897-2.

DOI:10.1038/s41598-023-28897-2
PMID:36732567
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9895067/
Abstract

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.

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,铁死亡参与了肿瘤的发展。同时,铁死亡相关基因(FRGs)与 NPC 的预后之间的联系尚不清楚。在本研究中,我们探讨了 NPC 正常对照和肿瘤样本之间失调的 FRGs。首先,与正常组织相比,NPC 组织中鉴定出 36 个差异表达 FRGs 中的 14 个,其中 ABCC1、GLS2、CS 和 HMGCR 与患者的预后不良相关。这四个铁死亡基因用于共识聚类分析,两个与风险相关的 FRGs(ABCC1 和 GLS2)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。多变量分析表明,风险评分和肿瘤内 TILs 是与预后相关的独立危险因素。此外,我们的结果表明风险特征与免疫微环境有关。此外,风险评分高的 NPC 患者对阿西替尼、多西他赛、恩贝林、埃博霉素.B、小白菊内酯、他普西隆、替吡法尼、长春瑞滨等化疗药物敏感。最后,使用免疫组织化学法验证了 NPC 组织中 ABCC1 和 GLS2 的表达。总之,这些结果表明铁死亡可能是 NPC 的一个潜在生物标志物,并为 NPC 的预后和治疗策略提供了有前途的未来方向。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9cc4/9895067/314a5e63b987/41598_2023_28897_Fig10_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9cc4/9895067/b71a63bc2b7e/41598_2023_28897_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9cc4/9895067/c283f26e6267/41598_2023_28897_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9cc4/9895067/7b585d408aac/41598_2023_28897_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9cc4/9895067/314a5e63b987/41598_2023_28897_Fig10_HTML.jpg

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