Department of Oncology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, 266000, China.
Hum Genomics. 2024 Nov 5;18(1):121. doi: 10.1186/s40246-024-00682-w.
Ferroptosis is a unique mode of cell death that is iron-dependent and associated with oxidative stress and lipid peroxidation. Oxidative stress and ferroptosis are essential mechanisms leading to metabolic abnormalities in cells and have been popular areas in cancer research.
Initially, 76 oxidative stress and ferroptosis-related genes (OFRGs) were acquired by intersecting the gene sets from oxidative stress and ferroptosis. Afterwards, optimal OFRGs were screened using PPI networks, and individuals were separated into two OFRG subtypes (K = 2). Subsequently, we successfully constructed and verified a prognostic signature comprising SLC7A2, Cadherin 19 (CDH19), and CCN1. To further uncover potential biomarkers of gastric cancer (GC), we examined the expression level of CDH19, investigated the effects of knocking down CDH19 on the biological behavior of GC cells, and explored whether CDH19 is involved in ferroptosis and oxidative stress processes.
According to the findings, individuals in the low-risk scoring group have less infiltration of immune suppressive cells, fewer occurrences of immune escape and dysfunction, greater efficacy in chemotherapy and immunotherapy, and better survival outcomes. The qRT-PCR assay indicated that CDH19 expression was significantly higher in GC cells. Through experiments, we demonstrated that knocking down CDH19 can affect the transcription levels of ACSL4 and GPX4, increase intracellular iron ion concentration and accumulation of reactive oxygen species (ROS), and inhibit the proliferation and migration of GC cells.
We developed an OFRG-related signature to predict the prognosis and treatment responsiveness of individuals with GC and identified CDH19 as a possible therapeutic target for GC.
铁死亡是一种独特的细胞死亡方式，依赖于铁，并与氧化应激和脂质过氧化有关。氧化应激和铁死亡是导致细胞代谢异常的重要机制，已成为癌症研究的热点领域。
首先，通过交集氧化应激和铁死亡相关基因集，获得 76 个氧化应激和铁死亡相关基因（OFRGs）。然后，利用 PPI 网络筛选最优 OFRGs，并将个体分为两种 OFRG 亚型（K=2）。随后，成功构建并验证了一个包含 SLC7A2、Cadherin 19（CDH19）和 CCN1 的预后标志物。为了进一步揭示胃癌（GC）的潜在生物标志物，我们检测了 CDH19 的表达水平，研究了敲低 CDH19 对 GC 细胞生物学行为的影响，并探讨了 CDH19 是否参与铁死亡和氧化应激过程。
根据研究结果，低风险评分组的个体中免疫抑制细胞浸润较少，免疫逃逸和功能障碍发生较少，化疗和免疫治疗效果更好，生存结局更好。qRT-PCR 检测结果显示，GC 细胞中 CDH19 的表达水平显著升高。通过实验，我们证明敲低 CDH19 可以影响 ACSL4 和 GPX4 的转录水平，增加细胞内铁离子浓度和活性氧（ROS）的积累，抑制 GC 细胞的增殖和迁移。
我们开发了一种 OFRG 相关的标志物来预测 GC 患者的预后和治疗反应，并确定 CDH19 可能是 GC 的一个治疗靶点。
