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识别头颈部鳞状细胞癌中的铜死亡相关亚型和肿瘤微环境特征。

Identification of cuproptosis-related subtypes and characterization of the tumor microenvironment landscape in head and neck squamous cell carcinoma.

机构信息

Department of Otolaryngology Head and Neck Surgery, Ningbo Medical Center Lihuili Hospital, The Affiliated Lihuili Hospital of Ningbo University, Ningbo, China.

School of Medicine, Ningbo University, Ningbo, China.

出版信息

J Clin Lab Anal. 2022 Sep;36(9):e24638. doi: 10.1002/jcla.24638. Epub 2022 Jul 31.

DOI:10.1002/jcla.24638
PMID:36082469
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9459342/
Abstract

BACKGROUND

Cuproptosis is considered a novel copper-dependent cell death model. In this study, we established a novel scoring system based on 10 cuproptosis-related genes (CRGs) to predict the prognosis and immune landscape of head and neck squamous cell carcinoma (HNSCC).

METHODS

The RNA-seq data of HNSCC patients were downloaded from the GEO and TCGA databases and were merged into a novel HNSCC cohort. Multiomics landscape analyses were conducted, including tumor mutation burden (TMB), copy number variations and the interaction network of CRGs. Patients were then divided into different cuproptosis subtypes based on the expression of 10 CRGs and subsequently regrouped into novel gene clusters referring to differentially expressed genes. A cuproptosis score (CS) system was established using principal component analysis. The CIBERSORT, ssGSEA and ESTIMATE algorithms were used to assess the tumor immune microenvironment. Moreover, the immunotherapeutic and chemotherapeutic responses were assessed.

RESULTS

Patients were divided into three cuproptosis subtypes and subsequently regrouped into three gene clusters, reflecting different immune infiltration. Assessed by the CS system, those with higher CSs exhibited worse prognosis and higher TMB frequency. Nevertheless, the immune-related analysis revealed patients in the low-CS group appeared immunosuppressive and easily suffered from immune escape. High CSs possibly show high expression of immune checkpoint genes and enhance chemotherapy sensitivity to cisplatin, docetaxel, and gemcitabine.

CONCLUSION

We established a novel scoring system to predict the prognosis and immune landscape of HNSCC patients. This signature exhibits satisfactory predictive effects and the potential to guide comprehensive treatment for patients.

摘要

背景

铜死亡被认为是一种新型的铜依赖性细胞死亡模型。在本研究中,我们基于 10 个铜死亡相关基因(CRGs)建立了一种新的评分系统,以预测头颈部鳞状细胞癌(HNSCC)的预后和免疫景观。

方法

从 GEO 和 TCGA 数据库下载 HNSCC 患者的 RNA-seq 数据,并将其合并为一个新的 HNSCC 队列。进行多组学景观分析,包括肿瘤突变负担(TMB)、拷贝数变异和 CRGs 的相互作用网络。然后,根据 10 个 CRGs 的表达将患者分为不同的铜死亡亚型,并随后根据差异表达基因重新分组为新的基因簇。使用主成分分析建立铜死亡评分(CS)系统。使用 CIBERSORT、ssGSEA 和 ESTIMATE 算法评估肿瘤免疫微环境。此外,还评估了免疫治疗和化疗反应。

结果

患者被分为三种铜死亡亚型,随后根据差异表达基因重新分为三种基因簇,反映了不同的免疫浸润。根据 CS 系统评估,CS 较高的患者预后较差,TMB 频率较高。然而,免疫相关分析表明,低 CS 组的患者表现出免疫抑制,容易发生免疫逃逸。高 CS 可能表现出免疫检查点基因的高表达,并增强对顺铂、多西他赛和吉西他滨的化疗敏感性。

结论

我们建立了一种新的评分系统来预测 HNSCC 患者的预后和免疫景观。该特征表现出令人满意的预测效果,并有潜力指导患者的综合治疗。

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