Chen Hui, Yu Yang, Zhou Lei, Chen Junliang, Li Zeyu, Tan Xiaodong
Department of General Surgery, Pancreatic, and Thyroid Ward, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China.
Front Genet. 2023 Jan 13;14:1049454. doi: 10.3389/fgene.2023.1049454. eCollection 2023.
Pancreatic cancer (PC) is a malignant gastrointestinal tumor with a terrible prognosis. Cuproptosis is a recently discovered form of cell death. This study is intended to explore the relationship between cuproptosis-related lncRNAs (CRLncs) signature with the prognosis and the tumor microenvironment (TME) of PC. Transcript sequencing data of PC samples with clinical information were obtained from the Cancer Genome Atlas (TCGA). Univariate Cox regression analysis and LASSO regression analysis were employed to construct the prognostic signature based on CRLncs associated with PC survival. A nomogram was created according to this signature, and the signaling pathway enrichment was analyzed. Subsequently, we explored the link between this prognostic signature with the mutational landscape and TME. Eventually, drug sensitivity was predicted based on this signature. Forty-six of 159 CRLncs were most significantly relevant to the prognosis of PC, and a 6-lncRNA prognostic signature was established. The expression level of signature lncRNAs were detected in PC cell lines. The AUC value of the ROC curve for this risk score predicting 5-year survival in PC was .944, which was an independent prognostic factor for PC. The risk score was tightly related to the mutational pattern of PC, especially the driver genes of PC. Single-sample gene set enrichment analysis (ssGSEA) demonstrated a significant correlation between signature with the TME of PC. Ultimately, compounds were measured for therapy in high-risk and low-risk PC patients, respectively. A prognostic signature of CRLncs for PC was established in the current study, which may serve as a promising marker for the outcomes of PC patients and has important forecasting roles for gene mutations, immune cell infiltration, and drug sensitivity in PC.
胰腺癌（PC）是一种预后极差的恶性胃肠道肿瘤。铜死亡是最近发现的一种细胞死亡形式。本研究旨在探讨铜死亡相关长链非编码RNA（CRLncs）特征与PC预后及肿瘤微环境（TME）之间的关系。从癌症基因组图谱（TCGA）获取了具有临床信息的PC样本的转录组测序数据。采用单因素Cox回归分析和LASSO回归分析，基于与PC生存相关的CRLncs构建预后特征。根据该特征创建了列线图，并分析了信号通路富集情况。随后，我们探讨了这种预后特征与突变图谱和TME之间的联系。最终，基于该特征预测了药物敏感性。159个CRLncs中的46个与PC的预后最显著相关，并建立了一个由6个lncRNA组成的预后特征。在PC细胞系中检测了特征lncRNAs的表达水平。该风险评分预测PC患者5年生存率的ROC曲线AUC值为0.944，是PC的独立预后因素。风险评分与PC的突变模式密切相关，尤其是PC的驱动基因。单样本基因集富集分析（ssGSEA）表明该特征与PC的TME之间存在显著相关性。最终，分别对高危和低危PC患者的化合物治疗效果进行了评估。本研究建立了PC的CRLncs预后特征，这可能是PC患者预后的一个有前景的标志物，对PC的基因突变、免疫细胞浸润和药物敏感性具有重要的预测作用。
