Comprehensive analysis of cuproptosis-related prognostic gene signature and tumor immune microenvironment in HCC.
Comprehensive analysis of cuproptosis-related prognostic gene signature and tumor immune microenvironment in HCC.
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DOI：
10.3389/fgene.2023.1094793
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发表时间：
2023
影响因子：
3.7
通讯作者：
Yang, Jun
中科院分区：
文献类型：
--
作者：
Qin, Haotian;Sheng, Weibei;Zhang, Geng;Yang, Qi;Yao, Sen;Yue, Yaohang;Zhang, Peng;Zhu, Yuanchao;Wang, Qichang;Chen, Yixiao;Zeng, Hui;Weng, Jian;Yu, Fei;Yang, Jun
关键词：
背景：铜是一种重要的矿物质元素，参与多种生理代谢过程。铜中毒与多种癌症相关，如肝细胞癌（HCC）。本研究旨在探讨肝细胞癌中铜中毒相关基因（CRG）的表达与肿瘤特征（包括预后和微环境）之间的关系。 研究方法：对肝癌组织中CRGs高表达组和低表达组的差异表达基因进行鉴定，并进一步进行功能富集分析。然后，构建HCC的CRG特征，并使用LASSO和单变量和多变量考克斯回归分析进行分析。通过Kaplan-Meier分析、独立预后分析和列线图评估CRG信号的预后价值。通过实时定量PCR（RT-qPCR）在HCC细胞系中验证预后CRG的表达。此外，使用一系列算法进一步探索HCC中预后CRGs表达与免疫浸润、肿瘤微环境、抗肿瘤药物反应和m6 A修饰之间的关系。最后，构建了基于预后CRG的ceRNA调控网络。 结果：CRG高表达组与低表达组之间的DEG主要富集于粘着斑和细胞外基质机化。此外，我们构建了一个由CDKN 2A、DLAT、DLST、GLS和PDHA 1 CRG组成的预测肝癌患者生存可能性的预后模型。这五种CRG在肝癌细胞系中的表达明显增高，且与预后不良有关。CRG高表达组患者的免疫评分和m6 A基因表达均高于正常对照组。此外，预后CRG在HCC中具有较高的突变率，并且与免疫细胞浸润、肿瘤突变负荷、微卫星不稳定性和抗肿瘤药物敏感性显著相关。预测了影响HCC进展的8个lncRNA-miRNA-mRNA调控轴。 结论：本研究表明CRG信号可以有效地评估HCC的预后、肿瘤免疫微环境、免疫治疗反应和预测lncRNA-miRNA-mRNA调控轴。这些发现扩展了我们对肝癌铜中毒的认识，并可能为肝癌的新治疗策略提供信息。
Background: Copper is an indispensable mineral element involved in many physiological metabolic processes. Cuproptosis is associated with a variety of cancer such as hepatocellular carcinoma (HCC). The objective of this study was to examine the relationships between the expression of cuproptosis-related genes (CRGs) and tumor characteristics, including prognosis and microenvironment of HCC. Methods: The differentially expressed genes (DEGs) between high and low CRGs expression groups in HCC samples were identified, and further were analyzed for functional enrichment analysis. Then, CRGs signature of HCC was constructed and analyzed utilizing LASSO and univariate and multivariate Cox regression analysis. Prognostic values of CRGs signature were evaluated by Kaplan-Meier analysis, independent prognostic analysis and nomograph. The expression of prognostic CRGs was verified by Real-time quantitative PCR (RT-qPCR) in HCC cell lines. In addition, the relationships between prognostic CRGs expression and the immune infiltration, tumor microenvironment, antitumor drugs response and m6A modifications were further explored using a series of algorithms in HCC. Finally, ceRNA regulatory network based on prognostic CRGs was constructed. Results: The DEGs between high and low CRG expression groups in HCC were mainly enriched in focal adhesion and extracellular matrix organization. Besides, we constructed a prognostic model that consists of CDKN2A, DLAT, DLST, GLS, and PDHA1 CRGs for predicting the survival likelihood of HCC patients. And the elevated expression of these five prognostic CRGs was substantially in HCC cell lines and associated with poor prognosis. Moreover, immune score and m6A gene expression were higher in the high CRG expression group of HCC patients. Furthermore, prognostic CRGs have higher mutation rates in HCC, and are significantly correlated with immune cell infiltration, tumor mutational burden, microsatellite instability, and anti-tumor drug sensitivity. Then, eight lncRNA-miRNA-mRNA regulatory axes that affected the progression of HCC were predicted. Conclusion: This study demonstrated that the CRGs signature could effectively evaluate prognosis, tumor immune microenvironment, immunotherapy response and predict lncRNA-miRNA-mRNA regulatory axes in HCC. These findings extend our knowledge of cuproptosis in HCC and may inform novel therapeutic strategies for HCC.
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影响因子：
7.3
作者：
Gao J;Aksoy BA;Dogrusoz U;Dresdner G;Gross B;Sumer SO;Sun Y;Jacobsen A;Sinha R;Larsson E;Cerami E;Sander C;Schultz N
通讯作者：
Schultz N
影响因子：
14.9
作者：
Chang, Le;Zhou, Guangyan;Xia, Jianguo
通讯作者：
Xia, Jianguo
铜稳态的改变是肝细胞癌对铜螯合敏感性的基础。
DOI：
10.1039/d0mt00156b
发表时间：
2020-12-23
期刊：
Metallomics : integrated biometal science
影响因子：
--
作者：
Davis CI;Gu X;Kiefer RM;Ralle M;Gade TP;Brady DC
通讯作者：
Brady DC
PM2.5通过翻译和转录激活DLAT介导的糖酵解重编程促进NSCLC癌变
DOI：
10.1186/s13046-022-02437-8
发表时间：
2022-07-22
期刊：
Journal of experimental & clinical cancer research : CR
影响因子：
--
作者：
通讯作者：
--
影响因子：
7.5
作者：
Ai, LB;Stephenson, KK;Fan, CY
通讯作者：
Fan, CY