Qu Jiaying, Yang Chunhui, Zhou Shunchen, Zhao Bosen, Tong Qiangsong, Zheng Liduan
Department of Pathology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China.
Department of Pediatric Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China.
Oncol Lett. 2025 Jul 14;30(3):440. doi: 10.3892/ol.2025.15186. eCollection 2025 Sep.
Gastric cancer is a global health challenge, necessitating the identification of novel biomarkers and therapeutic targets. The present study aimed to assess the role of cuproptosisrelated genes (CRGs) in gastric cancer, with the goal of establishing a predictive model consisting of key regulators with prognostic significance, thereby enabling the identification of key genes. Data from The Cancer Genome Atlas and Gene Expression Omnibus databases were used to analyze CRGs in stomach adenocarcinoma (STAD). Least absolute shrinkage and selection operator regression analysis was applied to create a risk model, and its predictive accuracy was confirmed for several clinical subgroups. Moreover, the prognostic value of essential regulators was evaluated through multiple analyses. A risk model with 15 CRGs was used to effectively predict STAD prognosis, demonstrating areas under the receiver operating characteristic curve values of 0.822, 0.811 and 0.922 for 1-, 3- and 5-year overall survival rates, respectively. The risk scores were associated with survival and tumor site. Among the CRGs, the gene for cytosolic iron-sulfur assembly component 1 () was revealed to be critical and associated with histological type, age and treatment outcome. Moreover, single-cell analysis demonstrated that is highly expressed in numerous types of cancer cells, and a high expression of was associated with upregulated transcription levels of immune checkpoints, increased tumor mutation load and decreased immune scores, highlighting its complex role in the tumor microenvironment. knockdown experiments were performed, and eliminating was associated with a reduction in the levels of iron-sulfur proteins and an increase in heat shock protein 70 expression, thereby inducing copper-dependent cell death. Furthermore, treatment with the drugs dasatinib and AT-9283 were associated with an inhibition of expression in gastric cancer cells, and decreased rates of tumor spread and invasion. Taken together, the findings of the present study suggest that is a promising biomarker both for assessing prognosis and evaluating the tumor immune microenvironment of gastric cancer.
胃癌是一项全球性的健康挑战，因此需要识别新的生物标志物和治疗靶点。本研究旨在评估铜死亡相关基因（CRGs）在胃癌中的作用，目标是建立一个由具有预后意义的关键调节因子组成的预测模型，从而识别关键基因。利用来自癌症基因组图谱（The Cancer Genome Atlas）和基因表达综合数据库（Gene Expression Omnibus）的数据来分析胃腺癌（STAD）中的CRGs。应用最小绝对收缩和选择算子回归分析来创建一个风险模型，并在几个临床亚组中证实了其预测准确性。此外，通过多种分析评估了关键调节因子的预后价值。一个包含15个CRGs的风险模型被用于有效预测STAD的预后，1年、3年和5年总生存率的受试者工作特征曲线下面积值分别为0.822、0.811和0.922。风险评分与生存率和肿瘤部位相关。在CRGs中，胞质铁硫组装成分1（）基因被证明至关重要，且与组织学类型、年龄和治疗结果相关。此外单细胞分析表明，在多种类型的癌细胞中高表达，并且的高表达与免疫检查点转录水平上调、肿瘤突变负荷增加和免疫评分降低相关，突出了其在肿瘤微环境中的复杂作用。进行了敲低实验，消除与铁硫蛋白水平降低和热休克蛋白70表达增加相关，从而诱导铜依赖性细胞死亡。此外，用达沙替尼和AT - 9283药物治疗与胃癌细胞中表达的抑制以及肿瘤扩散和侵袭率降低相关。综上所述，本研究结果表明，对于评估胃癌的预后和肿瘤免疫微环境而言，是一个有前景的生物标志物。
