He Chunmei, Zhang Hao, Guo Zehao, Mo Zhijing
School of Intelligent Medicine and Biotechnology, Guilin Medical University, Guilin, China.
J Gastrointest Oncol. 2023 Feb 28;14(1):146-164. doi: 10.21037/jgo-23-62.
Gastric cancer (GC) is one of the most common malignancies. Cuproptosis is a newly discovered type of cell death caused by protein toxicity stress, with copper having considerable importance in GC development.
First, differentially expressed (DE) cuproptosis-related genes (CRGs) were screened in GC. The tumor mutation burden (TMB) of CRGs was analyzed. We then performed enrichment analyses of DE-CRGs. Next, we constructed a GC cuproptosis-related (CR) signature (CRs) using Cox and least absolute shrinkage and selection operator (LASSO) regression analyses. The predictive efficacy was assessed using receiver operating characteristic (ROC) curves. Furthermore, we performed gene set enrichment analysis (GSEA). Different methods were used to assess tumor immunity of the CRs, and the Wilcoxon test was used to examine the expressions of . The "pRRophetic" R package (The R Foundation for Statistical Computing) was used to predict the half maximal inhibitory concentration IC50 of common chemotherapeutic agents. Finally, the expression of CRGs in different clusters was analyzed using single-cell RNA sequencing (scRNA-seq).
We identified 8 DE-CRGs in GC. There were 9 CRGs with TMB values >1%. We constructed gene expression networks and CRs for GC. The DE-CRGs were involved in important mitochondrial metabolic pathways, and the CRs was a valuable independent prognosis factor. The GSEA revealed that angiogenesis and metabolic-related pathways were enriched in the high-risk group, whereas the low-risk group showed enrichment in DNA replication mismatch and repair pathways. The expressions of immunological checkpoints, , type II interferon (INF) response, major histocompatibility complex (MHC class-I), and the IC50 of the copper-based carrier drug elesclomol were significantly different between the 2 groups of the CRs. Furthermore, the scRNA-seq analysis showed that most CRGs were mainly upregulated in endothelial cells.
The novel CRs could predict the prognosis of GC.
胃癌（GC）是最常见的恶性肿瘤之一。铜死亡是一种新发现的由蛋白质毒性应激引起的细胞死亡类型，铜在胃癌发生发展中具有重要意义。
首先，在胃癌中筛选差异表达的（DE）铜死亡相关基因（CRGs）。分析CRGs的肿瘤突变负担（TMB）。然后对DE-CRGs进行富集分析。接下来，使用Cox和最小绝对收缩与选择算子（LASSO）回归分析构建胃癌铜死亡相关（CR）特征（CRs）。使用受试者工作特征（ROC）曲线评估预测效能。此外，进行基因集富集分析（GSEA）。采用不同方法评估CRs的肿瘤免疫情况，使用Wilcoxon检验检测……的表达。使用“pRRophetic”R包（R统计计算基金会）预测常用化疗药物的半数最大抑制浓度IC50。最后，使用单细胞RNA测序（scRNA-seq）分析不同簇中CRGs的表达。
我们在胃癌中鉴定出8个DE-CRGs。有9个CRGs的TMB值>1%。我们构建了胃癌的基因表达网络和CRs。DE-CRGs参与重要的线粒体代谢途径，CRs是一个有价值的独立预后因素。GSEA显示，高危组中血管生成和代谢相关途径富集，而低危组在DNA复制错配和修复途径中富集。两组CRs之间免疫检查点、……、II型干扰素（INF）反应、主要组织相容性复合体（MHC-I类）的表达以及铜基载体药物依斯氯铵的IC50存在显著差异。此外，scRNA-seq分析表明，大多数CRGs主要在内皮细胞中上调。
新的CRs可预测胃癌的预后。
