识别和评估二硫下垂相关基因特征以预测结直肠腺癌患者的预后。
Identifying and evaluating a disulfidptosis-related gene signature to predict prognosis in colorectal adenocarcinoma patients.
发表日期:2024
作者:
Ming Li, Jin Wang, Yuhao Zhao, Changjie Lin, Jianqing Miao, Xiaoming Ma, Zhenyu Ye, Chao Chen, Ke Tao, Pengcheng Zhu, Qi Hu, Jinbing Sun, Jianfeng Gu, Shaohua Wei
来源:
Frontiers in Immunology
摘要:
二硫下垂症是一种受调节的细胞死亡形式,最近报道在以 SLC7A11 高表达为特征的癌症中,包括浸润性乳腺癌、肺腺癌和肝细胞癌。然而,它在结肠腺癌(COAD)中的作用却很少被讨论。在这项研究中,我们使用 LASSO 和 Cox 回归分析开发并验证了基于 20 个二硫下垂相关基因 (DRG) 的预后模型。通过列线图评估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、几个关键的癌症相关生物过程、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性,可能充当癌基因。体外测定表明,POU4F1 敲低显着降低了 COAD 细胞的细胞增殖和迁移,但增加了细胞衰老。我们通过在缺糖培养基中培养细胞进一步研究了 DRG 在二硫下垂中的调节作用。综上所述,我们的研究揭示并证实了基于 DRG 的 COAD 患者风险预测模型,验证了 POU4F1 在促进细胞增殖、迁移和二硫下垂中的作用。版权所有 © 2024 Li、Wang、Zhao、Lin、Miao、Ma、Ye 、陈、陶、朱、胡、孙、顾、韦。
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. In vitro 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.Copyright © 2024 Li, Wang, Zhao, Lin, Miao, Ma, Ye, Chen, Tao, Zhu, Hu, Sun, Gu and Wei.