A novel cuproptosis-related gene signature of prognosis and immune microenvironment in head and neck squamous cell carcinoma cancer
作者全名："Jiang, Xu; Ke, Jing; Jia, Lifeng; An, Xiang; Ma, Haiyu; Li, Zhongwan; Yuan, Wei"
作者地址："[Jiang, Xu; Ke, Jing; Jia, Lifeng; An, Xiang; Ma, Haiyu; Li, Zhongwan; Yuan, Wei] Chongqing Gen Hosp, Dept Otorhinolaryngol Head & Neck Surg, 118 Xingguang Ave, Chongqing 401147, Peoples R China; [Jiang, Xu; Ke, Jing; Jia, Lifeng; An, Xiang; Ma, Haiyu; Li, Zhongwan; Yuan, Wei] Univ Chinese Acad Sci SCAS Chongqing, Chongqing Hosp, Dept Otorhinolaryngol Head & Neck Surg, Chongqing, Peoples R China; [Ke, Jing; Yuan, Wei] Chongqing Med Univ, Chongqing, Peoples R China"
通信作者："Yuan, W (通讯作者)，Chongqing Gen Hosp, Dept Otorhinolaryngol Head & Neck Surg, 118 Xingguang Ave, Chongqing 401147, Peoples R China.; Yuan, W (通讯作者)，Univ Chinese Acad Sci SCAS Chongqing, Chongqing Hosp, Dept Otorhinolaryngol Head & Neck Surg, Chongqing, Peoples R China.; Yuan, W (通讯作者)，Chongqing Med Univ, Chongqing, Peoples R China."
来源：JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
ESI学科分类：CLINICAL MEDICINE
WOS号：WOS:000884527200003
JCR分区：Q2
影响因子：3.6
年份：2022
卷号：
期号：
开始页：
结束页：
文献类型：Article; Early Access
关键词：Cuproptosis; HNSCC; Risk model; Overall survival; Immune infiltration
摘要："Background Cuproptosis is a novel form of cell death that is highly related to mitochondrial metabolism and mediated by protein lipoacetylation. This study systematically assessed the differential expression and genetic alterations of cuproptosis-related genes (CRGs) in head and neck squamous-cell carcinoma (HNSCC) and constructed CRG risk models to predict survival in patients with HNSCC. Methods We investigated the expression of 19 CRGs in HNSCC and noncancerous tissues, and the relationship between mutation load, immune infiltration, and clinical features was examined based on data from public databases. CRG risk models were constructed by univariate Cox analysis and lasso regression and validated by independent datasets for their accuracy in predicting survival outcomes in patients with HNSCC. The expression distribution of CRGs in HNSCC cells was further explored in the HNSCC single-cell sequencing dataset. Results NFE2L2, ATP7A, FDX1, LIAS, DLD, DLAT, PDHB, MTF1 and DBT were highly expressed in noncancerous samples, while GLS, CDKN2A and DLST were highly expressed in HNSCC samples (p < 0.05). Gene copy number variation frequency (CNV) revealed CDKN2A, FDX1 and DLAT copy number deletions and LIPT2 and NFE2L2 copy number increases. Ten CRGs were used to construct a risk model to predict overall survival (OS) in HNSCC, yielding reduced OS in the high-risk group compared to the low-risk group, training group (p = 9.733e - 05), and testing group (p = 0.040). The CRG risk model was significantly correlated with various immune cells, regulatory T cells (Tregs) and memory B cells were significantly negatively correlated (p = 0.027, p = 0.00084), and resting CD4 memory T cells was significantly positively correlated (p = 9e - 04). Most CRGs significantly affected the clinical characteristics of HNSCC. NFE2L2, SLC31A1, PDHA1, CDKN2A and DBT were highly expressed in epithelial cells of HNSCC, while SLC31A1, DBT and NFE2L2 were highly expressed in T cells, and SLC31A1 in B cells. In monocytes, NFE2L2, SLC31A1 and PDHA1 were highly expressed. Conclusion The CRG risk model can be used as a potential prognostic factor for HNSCC patients and may provide new insights into cancer treatment from the perspective of copper metabolism."
基金机构："Chongqing Municipal Health and Wellness Commission [2021MSXM018]; Chongqing Medical University Postgraduate Research Innovation Project, Clinical and experimental study of terahertz time-domain system in the determination of pathological margin of laryngeal carcinoma [CYS21253]"
基金资助正文："This work was supported by the Chongqing Municipal Health and Wellness Commission, Clinical and experimental study of terahertz time-domain system in judging pathological margin of hypopharyngeal carcinoma, [2021MSXM018]. A grant from the Chongqing Medical University Postgraduate Research Innovation Project, Clinical and experimental study of terahertz time-domain system in the determination of pathological margin of laryngeal carcinoma, [CYS21253]."
