Li Jiazheng, Kong Can, Song Wei, Fu Tao
Department of Gastrointestinal Surgery, Renmin Hospital of Wuhan University, Wuhan, People's Republic of China.
Department of General Surgery, Qingdao Municipal Hospital, Qingdao, People's Republic of China.
Int J Gen Med. 2023 May 2;16:1631-1652. doi: 10.2147/IJGM.S404847. eCollection 2023.
Cuproptosis is a newly identified form of programmed cell death. We aimed to comprehensively discuss the correlation of cuproptosis with gastric cancer (GC) using bioinformatic methods.
This study selected GC bulk and single-cell RNA sequencing profiles from public databases. Based on the enrichment pattern of cuproptosis-related gene sets (CRGSs), GC patients were classified into different cuproptosis subtypes. A series of systematic analyses was performed to investigate the correlation of cuproptosis subtype with biological function and immune cell infiltration. In addition, we established a CRGS risk score signature to quantify GC patients' risk level, and analyzed the signature's relationship with clinical features, tumor microenvironment (TME) and treatment responses. Genes used for the construction of the risk score model were also detected in GC tumor and normal tissues by real-time quantitative polymerase chain reaction (RT-qPCR).
First, analysis of scRNA-seq data revealed the alterations in CRGS enrichment scores for patients with GC and precancerous diseases. Then, based on large GC patient cohorts, two cuproptosis subtypes with significant differences in survival, biological function and TME were identified. Furthermore, we established a CRGS risk score signature. High-risk patients on the CRGS risk score signature with worse overall survival were characterized by higher immune and stromal contents in the TME, more advanced clinicopathological features, and better sensitivity to a wider range of anti-tumor drugs. Low-risk patients were correlated with higher tumor purity, and demonstrated more favorable clinical outcomes and higher sensitivity to immunotherapy.
The current work elucidated that cuproptosis plays an important role in the regulation of TME landscapes in GC. Two cuproptosis subtypes with distinct TME characteristics were identified. In addition, the establishment of a CRGS risk score signature could provide novel insights into accurate prediction and personalized treatment for GC patients.
铜死亡是一种新发现的程序性细胞死亡形式。我们旨在使用生物信息学方法全面探讨铜死亡与胃癌（GC）的相关性。
本研究从公共数据库中选取了GC的批量和单细胞RNA测序图谱。基于铜死亡相关基因集（CRGSs）的富集模式，将GC患者分为不同的铜死亡亚型。进行了一系列系统分析，以研究铜死亡亚型与生物学功能和免疫细胞浸润的相关性。此外，我们建立了一个CRGS风险评分特征来量化GC患者的风险水平，并分析了该特征与临床特征、肿瘤微环境（TME）和治疗反应的关系。还通过实时定量聚合酶链反应（RT-qPCR）在GC肿瘤组织和正常组织中检测了用于构建风险评分模型的基因。
首先，对scRNA-seq数据的分析揭示了GC患者和癌前疾病患者CRGS富集分数的变化。然后，基于大量GC患者队列，确定了两种在生存、生物学功能和TME方面存在显著差异的铜死亡亚型。此外，我们建立了一个CRGS风险评分特征。CRGS风险评分特征高风险的患者总生存期较差，其特征是TME中的免疫和基质成分较高、临床病理特征更晚期，并且对更广泛的抗肿瘤药物更敏感。低风险患者与更高的肿瘤纯度相关，并且表现出更有利的临床结果和对免疫治疗更高的敏感性。
目前的研究阐明了铜死亡在GC的TME景观调节中起重要作用。确定了两种具有不同TME特征的铜死亡亚型。此外，CRGS风险评分特征的建立可为GC患者的准确预测和个性化治疗提供新的见解。
