Deng Qianxi, Yang Kun, Liao Qiaoling, Tang Xueli, Quan Honglin, Yuan Guojun, Hu Xia, Jiang Zheng, Wu Linju
Department of Gastroenterology, The Third Hospital of Mianyang (Sichuan Mental Health Center), Mianyang, Sichuan, China.
Department of Gastroenterology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
PLoS One. 2025 May 14;20(5):e0323458. doi: 10.1371/journal.pone.0323458. eCollection 2025.
Cuproposis is a new-found mechanism of cell death, and the role of cuproposis-related genes (CRGs) in pancreatic cancer prognosis remains uncertain.
DECRGs were identified from TCGA and GTEx databases. Five OS-associated hub genes were screened using Cox regression and LASSO analyses. A prognostic model was constructed and validated by survival analysis. GSEA, gene mutation, small-molecule drugs, immune-infiltrating and TF/miRNA/mRNA network were investigated to determine the underlying mechanism of 5-CRGs. In addition, RT-qPCR, and WB were applied to validate the expression of 5-CRGs. CCK8, colony formation and transwell assays were used to prove the function of LIPT1 in PC.
PDP1, DLAT, DBT, LIAS, and LIPT1 were screened as hub genes. 5-CRGs prognostic model established the low-risk population has a longer OS. There was a high the risk score value for the prediction in clinicopathological features. The forest plots showed that age, N stage and the RiskScore were the significant independent risk indicators. T cells CD4 memory resting and Mast cells are the amplest immune cell subpopulations in the high-score individuals. The expression of 5 CRGs exhibited significant differences in PC cell lines and tissues, LIPT1-knockdowning inhibited proliferation and invasion of pancreatic cancer cell lines.
Five CRGs relevant to pancreatic cancer prognosis were identified. Meanwhile, a new and accurate five CRGs prognostic model of pancreatic cancer was constructed. In addition, LIPT1 may promote proliferation, invasion and migration of pancreatic cancer cell lines. This may have a specific guiding value for future development of precise anti-cancer treatment strategies.
铜死亡是一种新发现的细胞死亡机制，铜死亡相关基因（CRGs）在胰腺癌预后中的作用仍不明确。
从TCGA和GTEx数据库中鉴定出DECRGs。使用Cox回归和LASSO分析筛选出5个与总生存期（OS）相关的枢纽基因。构建预后模型并通过生存分析进行验证。进行基因集富集分析（GSEA）、基因突变、小分子药物、免疫浸润和转录因子/微小RNA/信使RNA网络研究，以确定5个CRGs的潜在机制。此外，应用逆转录定量聚合酶链反应（RT-qPCR）和蛋白质免疫印迹法（WB）验证5个CRGs的表达。采用细胞计数试剂盒-8（CCK8）、集落形成和Transwell实验来证明脂酰辅酶A合成酶1（LIPT1）在胰腺癌中的功能。
丙酮酸脱氢酶磷酸酶1（PDP1）、二氢硫辛酰胺转乙酰基酶（DLAT）、二氢硫辛酰胺转琥珀酰基酶（DBT）、硫辛酸合成酶（LIAS）和LIPT1被筛选为枢纽基因。5个CRGs预后模型显示低风险人群的总生存期更长。临床病理特征预测的风险评分值较高。森林图显示年龄、N分期和风险评分是显著的独立风险指标。T细胞CD4记忆静止细胞和肥大细胞是高分个体中最丰富的免疫细胞亚群。5个CRGs在胰腺癌细胞系和组织中的表达存在显著差异，敲低LIPT1可抑制胰腺癌细胞系的增殖和侵袭。
鉴定出5个与胰腺癌预后相关的CRGs。同时，构建了一种新的、准确的胰腺癌5个CRGs预后模型。此外，LIPT1可能促进胰腺癌细胞系的增殖、侵袭和迁移。这可能对未来精准抗癌治疗策略的发展具有特定的指导价值。
