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一种新型与铜死亡相关的长链非编码 RNA 预后标志物,用于预测头颈部鳞状细胞癌的治疗和免疫环境。

A novel cuproptosis-related lncRNA prognostic signature for predicting treatment and immune environment of head and neck squamous cell carcinoma.

机构信息

Zhongshan Clinical College, Dalian University, Dalian 116000, China.

Medical College, Guangxi University, Nanning 530000, China.

出版信息

Math Biosci Eng. 2022 Aug 19;19(12):12127-12145. doi: 10.3934/mbe.2022564.

DOI:10.3934/mbe.2022564
PMID:36653989
Abstract

Head and neck squamous cell carcinoma (HNSCC) is an urgent public health issue due to its poor prognosis and resistance to anti-cancer agents. However, the role of cuproptosis, a newly identified form cell death, in applications of HNSCC is still not a known. In this study, single-cell RNA sequencing data was used to explore cuproptosis-related gene expression in the tumour microenvironment. A prognostic model was constructed based on the cuproptosis-related lncRNA. Various methods were performed to predict the overall survival (OS) of different risk score patients and explore difference in enrichment function and pathways between the risk score patients. Finally, a series of immunogenomic landscape analyses were performed and evaluated the immune function, immune infiltration and sensitivity to chemotherapeutic agents. Cancer cell cluster expressed the essential cuproptosis-related gene. As the risk score increased of HNSCC patients, a significant decrease in survival status and time occurred for patients in the high-risk score patient. The AUC for predicting 1-, 3-, and 5-years OS were 0.679, 0.713 and 0.656, indicating that the model regarded as an independent prognostic signature in comparison with the clinical-pathological characteristics. As a results of GO, the immune function and immune infiltration of different risk score patients were assessed, revealing significant differences in T cell function and abundance of different types of T cells. Low-risk score patients are relatively insensitive to chemotherapy agents such as docetaxel and cisplatin, and easily resistant to immunotherapy. A cuproptosis-related lncRNA prognostic model was constructed to predict OS of HNSCC patients and provided the newly therapeutic strategies.

摘要

头颈部鳞状细胞癌(HNSCC)由于预后不良和对抗癌药物的耐药性,是一个紧迫的公共卫生问题。然而,细胞死亡的一种新形式——铜死亡,在 HNSCC 中的应用作用尚不清楚。在本研究中,使用单细胞 RNA 测序数据来探索肿瘤微环境中的铜死亡相关基因表达。基于铜死亡相关 lncRNA 构建了预后模型。采用各种方法预测不同风险评分患者的总生存期(OS),并探讨风险评分患者之间富集功能和途径的差异。最后,进行了一系列免疫基因组景观分析,并评估了免疫功能、免疫浸润和对化疗药物的敏感性。癌细胞簇表达了必需的铜死亡相关基因。随着 HNSCC 患者的风险评分增加,高风险评分患者的生存状态和时间显著下降。预测 1 年、3 年和 5 年 OS 的 AUC 分别为 0.679、0.713 和 0.656,表明该模型被认为是与临床病理特征相比的独立预后标志物。作为 GO 的结果,评估了不同风险评分患者的免疫功能和免疫浸润,揭示了 T 细胞功能和不同类型 T 细胞丰度的显著差异。低风险评分患者对多西他赛和顺铂等化疗药物相对不敏感,容易对免疫疗法产生耐药性。构建了铜死亡相关 lncRNA 预后模型来预测 HNSCC 患者的 OS,并提供了新的治疗策略。

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