Dong Hao, Zhao Shutao, Zhang Chao, Wang Xudong
Department of Gastrointestinal Nutrition and Hernia Surgery, The Second Hospital of Jilin University, Changchun, China.
Front Surg. 2023 Jan 6;9:991624. doi: 10.3389/fsurg.2022.991624. eCollection 2022.
Cuprotosis is a novel mechanism of cell death that differs from known mechanisms, which depends on mitochondrial respiration and is closely related to lipoylated components of the tricarboxylic acid (TCA) cycle. However, it is unclear whether cuprotosis-related genes (CRGs) affect the tumor microenvironment (TME) and prognosis of patients with gastric cancer. In this study, the genetic and transcriptional characteristics of CRGs in gastric cancer (GC) were analyzed, and five CRGs that were differentially expressed and correlated with the survival of patients were obtained. Two different molecular subtypes were identified according to the five CRGs. Then, we constructed a CRG_score applied to patients of any age, gender, and stage. Subsequently, we found that cluster B and a high CRG_score had a worse prognosis, fewer immune checkpoints, and higher tumor immune dysfunction and exclusion (TIDE) compared to cluster A and a low CRG_score. In addition, two subtypes and the CRG_score were closely associated with clinicopathological characteristics, human leukocyte antigens (HLAs) and TME cell infiltration. A high CRG_score was featured with decreased microsatellite instability-high (MSI-H) and mutational burden. Meanwhile, the CRG_score was significantly related to the cancer stem cell (CSC) index and chemotherapeutic response. Moreover, we developed a nomogram to predict the survival probability of patients. Our study explained the role of CRGs in GC, and the prognostic signature could potentially provide an approach for personalized tumor therapy.
铜死亡是一种不同于已知机制的新型细胞死亡机制，其依赖于线粒体呼吸作用，且与三羧酸（TCA）循环的脂酰化成分密切相关。然而，尚不清楚铜死亡相关基因（CRGs）是否会影响胃癌患者的肿瘤微环境（TME）和预后。在本研究中，分析了胃癌（GC）中CRGs的遗传和转录特征，获得了五个差异表达且与患者生存相关的CRGs。根据这五个CRGs鉴定出两种不同的分子亚型。然后，我们构建了一个适用于任何年龄、性别和分期患者的CRG_score。随后，我们发现与A组和低CRG_score相比，B组和高CRG_score的预后更差，免疫检查点更少，肿瘤免疫功能障碍和排除（TIDE）更高。此外，两种亚型和CRG_score与临床病理特征、人类白细胞抗原（HLAs）和TME细胞浸润密切相关。高CRG_score的特征是微卫星高度不稳定（MSI-H）和突变负担降低。同时，CRG_score与癌症干细胞（CSC）指数和化疗反应显著相关。此外，我们开发了一种列线图来预测患者的生存概率。我们的研究解释了CRGs在胃癌中的作用，并且该预后标志物可能为个性化肿瘤治疗提供一种方法。
