Department of General Surgery, The Second Affiliated Hospital of Soochow University, Suzhou, China.
Department of General Surgery, Changshu Hospital Affiliated to Soochow University, The First People's Hospital of Changshu, Changshu, Jiangsu, China.
Front Immunol. 2024 Jun 19;15:1344637. doi: 10.3389/fimmu.2024.1344637. eCollection 2024.
Disulfidptosis, a regulated form of cell death, has been recently reported in cancers characterized by high SLC7A11 expression, including invasive breast carcinoma, lung adenocarcinoma, and hepatocellular carcinoma. However, its role in colon adenocarcinoma (COAD) has been infrequently discussed. In this study, we developed and validated a prognostic model based on 20 disulfidptosis-related genes (DRGs) using LASSO and Cox regression analyses. The robustness and practicality of this model were assessed via a nomogram. Subsequent correlation and enrichment analysis revealed a relationship between the risk score, several critical cancer-related biological processes, immune cell infiltration, and the expression of oncogenes and cell senescence-related genes. POU4F1, a significant component of our model, might function as an oncogene due to its upregulation in COAD tumors and its positive correlation with oncogene expression. assays demonstrated that POU4F1 knockdown noticeably decreased cell proliferation and migration but increased cell senescence in COAD cells. We further investigated the regulatory role of the DRG in disulfidptosis by culturing cells in a glucose-deprived medium. In summary, our research revealed and confirmed a DRG-based risk prediction model for COAD patients and verified the role of POU4F1 in promoting cell proliferation, migration, and disulfidptosis.
二硫键程序性细胞死亡(Disulfidptosis)是一种受调控的细胞死亡形式,最近在 SLC7A11 高表达的癌症中被报道,包括浸润性乳腺癌、肺腺癌和肝细胞癌。然而,其在结肠腺癌(COAD)中的作用尚未得到充分讨论。在这项研究中,我们使用 LASSO 和 Cox 回归分析开发并验证了一个基于 20 个二硫键程序性细胞死亡相关基因(DRGs)的预后模型。通过列线图评估了该模型的稳健性和实用性。随后的相关性和富集分析揭示了风险评分与几个关键的癌症相关生物学过程、免疫细胞浸润以及癌基因和细胞衰老相关基因的表达之间的关系。POU4F1 是我们模型的一个重要组成部分,由于其在 COAD 肿瘤中的上调及其与癌基因表达的正相关,可能作为一个癌基因发挥作用。细胞增殖和迁移,但增加了 COAD 细胞的衰老。我们进一步通过在葡萄糖剥夺培养基中培养细胞来研究 DRG 在二硫键程序性细胞死亡中的调节作用。总之,我们的研究揭示并证实了一个基于 DRG 的 COAD 患者风险预测模型,并验证了 POU4F1 在促进细胞增殖、迁移和二硫键程序性细胞死亡中的作用。