Liu Jiangtao, Xia Wei, Xue Feng, Xu Chen
General Surgery, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, China.
Department of Vasculocardiology, Yangzhou Friendship Hospital, Yangzhou, 225009, China.
Discov Oncol. 2024 Sep 29;15(1):508. doi: 10.1007/s12672-024-01389-z.
Lung adenocarcinoma (LUAD) continues to pose a significant global health challenge. This research investigates cuproptosis and its association with LUAD progression. Employing various bioinformatics techniques, the study explores the heterogeneity of LUAD cells, identifies prognostic cuproptosis-related genes (CRGs), examines cell-to-cell communication networks, and assesses their functional roles.
We downloaded single-cell RNA sequencing data from TISCH2 and bulk RNA sequencing data from TCGA for exploring LUAD cell heterogeneity. Subsequently, "CellChat" package was employed for intercellular communication network analysis, while weighted correlation network analysis was applied for identification of hub CRGs. Further, A cuproptosis related prognostic signature was constructed via LASSO regression, validated through survival analysis, nomogram development, and ROC curves. We assessed immune infiltration, gene mutations, and GSEA of prognostic CRGs. Finally, in vitro experiments were applied to validate CDC25C's role in LUAD.
We identified 15 clusters and nine cell type in LUAD. Malignant cells showed active communication and pathway enrichment in "oxidative phosphorylation" and "glycolysis". Meanwhile, prognostic hub CRGs including PFKP, CDC25C, F12, SIGLEC6, and NLRP7 were identified, with a robust prognostic signature. Immune infiltration, gene mutations, and functional enrichment correlated with prognostic CRGs. In vitro cell experiments have shown that CDC25C-deficient LUAD cell lines exhibited reduced activity.
This research reveals the heterogeneity of LUAD cells, identifies key prognostic CRGs, and maps intercellular communication networks, providing insights into LUAD pathogenesis. These findings pave the way for developing targeted therapies and precision medicine approaches.
肺腺癌（LUAD）仍然是一项重大的全球健康挑战。本研究调查铜死亡及其与LUAD进展的关联。该研究采用各种生物信息学技术，探索LUAD细胞的异质性，识别与铜死亡相关的预后基因（CRGs），检查细胞间通信网络，并评估它们的功能作用。
我们从TISCH2下载了单细胞RNA测序数据，并从TCGA下载了批量RNA测序数据，以探索LUAD细胞的异质性。随后，使用“CellChat”软件包进行细胞间通信网络分析，同时应用加权相关网络分析来识别核心CRGs。此外，通过LASSO回归构建了一个与铜死亡相关的预后特征，并通过生存分析、列线图构建和ROC曲线进行验证。我们评估了预后CRGs的免疫浸润、基因突变和基因集富集分析（GSEA）。最后，进行体外实验以验证细胞周期蛋白磷酸酶25C（CDC25C）在LUAD中的作用。
我们在LUAD中识别出15个细胞簇和9种细胞类型。恶性细胞在“氧化磷酸化”和“糖酵解”中表现出活跃的通信和通路富集。同时，识别出了包括磷酸果糖激酶P（PFKP）、CDC25C、凝血因子XII（F12）、唾液酸结合免疫球蛋白样凝集素6（SIGLEC6）和NLR家族含pyrin结构域蛋白7（NLRP7）在内的预后核心CRGs，并具有强大的预后特征。免疫浸润、基因突变和功能富集与预后CRGs相关。体外细胞实验表明，缺乏CDC25C的LUAD细胞系活性降低。
本研究揭示了LUAD细胞的异质性，识别出关键的预后CRGs，并绘制了细胞间通信网络，为LUAD发病机制提供了见解。这些发现为开发靶向治疗和精准医学方法铺平了道路。
