Liu Shuang, Xiao Chunmei, Rong Yue, Liu Mingbo, Yang Ke, Tang Jing, Wang Zhigang
Department of Ultrasound, Women and Children's Hospital of Chongqing Medical University No. 120, Longshan Road, Yubei Distinct, Chongqing 401147, China.
Department of Obstetrics and Gynecology, Chongqing Health Center for Women and Children, Women and Children's Hospital of Chongqing Medical University No. 120, Longshan Road, Yubei District, Chongqing 401147, China.
Am J Cancer Res. 2024 Oct 15;14(10):4686-4707. doi: 10.62347/ONUY8904. eCollection 2024.
Ovarian cancer (OC) is a common gynecological malignant tumor with poor prognosis. One form of controlled cell death that requires iron is ferroptosis. This study utilized TCGA data analysis to identify differentially expressed genes (DEGs) related to ferroptosis in OC, revealing 2,333 up-regulated and 4,073 down-regulated genes. Venn diagrams identified 64 up-regulated and 120 down-regulated ferroptosis-related DEGs (FR-DEGs), with 15 showing a significant correlation with overall patient survival. Further analyses explored the expression, mutations, and copy number variations of these 15 FR-DEGs across various cancer types, constructing interaction networks. Molecular subtypes in OC were classified using these 15 FR-DEGs, revealing two subtypes (C1 and C2). Survival analysis identified a risk model for the C1 group based on these genes. Experimental validation highlighted TRIM46 as a key gene, with knockdown inhibiting OC cell proliferation and migration. TRIM46 was also associated with changes in ferroptosis-related markers and demonstrated a close connection with the Wnt signaling pathway, validated through Western blot experiments. Overall, the study provided a comprehensive understanding of the role of DEGs related to ferroptosis in OC, offering valuable insights into disease mechanisms and potential therapeutic targets.
卵巢癌(OC)是一种常见的妇科恶性肿瘤,预后较差。一种需要铁的程序性细胞死亡形式是铁死亡。本研究利用TCGA数据分析来鉴定OC中与铁死亡相关的差异表达基因(DEGs),发现2333个上调基因和4073个下调基因。维恩图确定了64个上调和120个下调的铁死亡相关DEGs(FR-DEGs),其中15个与患者总生存期显著相关。进一步分析探讨了这15个FR-DEGs在各种癌症类型中的表达、突变和拷贝数变异,构建了相互作用网络。利用这15个FR-DEGs对OC中的分子亚型进行分类,发现了两个亚型(C1和C2)。生存分析基于这些基因确定了C1组的风险模型。实验验证突出了TRIM46作为关键基因,敲低该基因可抑制OC细胞增殖和迁移。TRIM46还与铁死亡相关标志物的变化有关,并通过蛋白质印迹实验证实与Wnt信号通路密切相关。总体而言,该研究全面了解了OC中与铁死亡相关的DEGs的作用,为疾病机制和潜在治疗靶点提供了有价值的见解。