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鉴定一种与铜死亡相关的新型基因特征对头颈部鳞状细胞癌预后的影响

Identification of a Novel Cuproptosis-Related Gene Signature for Prognostic Implication in Head and Neck Squamous Carcinomas.

作者信息

Tang Shouyi, Zhao Li, Wu Xing-Bo, Wang Zhen, Cai Lu-Yao, Pan Dan, Li Ying, Zhou Yu, Shen Yingqiang

机构信息

State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Chinese Academy of Medical Sciences Research Unit of Oral Carcinogenesis and Management, West China Hospital of Stomatology, Sichuan University, Chengdu 640041, China.

State Institute of Drug/Medical Device Clinical Trial, West China Hospital of Stomatology, Chengdu 610041, China.

出版信息

Cancers (Basel). 2022 Aug 18;14(16):3986. doi: 10.3390/cancers14163986.

Abstract

Head and neck squamous carcinoma (HNSC) is a frequent and deadly malignancy that is challenging to manage. The existing treatment options have considerable efficacy limitations. Hence, the identification of new therapeutic targets and the development of efficacious treatments are urgent needs. Cuproptosis, a non-apoptotic programmed cell death caused by excess copper, has only very recently been discovered. The present study investigated the prognostic importance of genes involved in cuproptosis through the mRNA expression data and related clinical information of HNSC patients downloaded from public databases. Our results revealed that many cuproptosis-related genes were differentially expressed between normal and HNSC tissues in the TCGA cohort. Moreover, 39 differentially expressed genes were associated with the prognosis of HNSC patients. Then, a 24-gene signature was identified in the TCGA cohort utilizing the LASSO Cox regression model. HNSC expression data used for validation were obtained from the GEO database. Consequently, we divided patients into high- and low-risk groups based on the 24-gene signature. Furthermore, we demonstrated that the high-risk group had a worse prognosis when compared to the low-risk group. Additionally, significant differences were found between the two groups in metabolic pathways, immune microenvironment, etc. In conclusion, we found a cuproptosis-related gene signature that can be used effectively to predict OS in HNSC patients. Thus, targeting cuproptosis might be an alternative and promising strategy for HNSC patients.

摘要

头颈部鳞状细胞癌(HNSC)是一种常见且致命的恶性肿瘤,治疗颇具挑战性。现有的治疗方案存在相当大的疗效局限性。因此,识别新的治疗靶点并开发有效的治疗方法是当务之急。铜死亡是一种由过量铜引起的非凋亡程序性细胞死亡,直到最近才被发现。本研究通过从公共数据库下载的HNSC患者的mRNA表达数据和相关临床信息,研究了与铜死亡相关基因的预后重要性。我们的结果显示,在TCGA队列中,许多与铜死亡相关的基因在正常组织和HNSC组织之间存在差异表达。此外,39个差异表达基因与HNSC患者的预后相关。然后,利用LASSO Cox回归模型在TCGA队列中确定了一个24基因特征。用于验证的HNSC表达数据来自GEO数据库。因此,我们根据24基因特征将患者分为高风险组和低风险组。此外,我们证明高风险组的预后比低风险组更差。此外,两组在代谢途径、免疫微环境等方面存在显著差异。总之,我们发现了一个与铜死亡相关的基因特征,可有效用于预测HNSC患者的总生存期。因此,针对铜死亡可能是HNSC患者的一种替代且有前景的策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ccfa/9406337/a2574cb6c862/cancers-14-03986-g001.jpg

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