Zhu Dan, Zhu Yamei, Liu Lin, He Xiaoxue, Fu Shizhong
Xinqiao Hospital, Army Medical University (Third Military Medical University), Chongqing, China.
Deptartment of Infectious Diseases, Wuhua Ward, 920th Hospital of Joint Logistics Support Force of Chinese PLA, Kunming, Yunnan, China.
Front Neurol. 2023 Mar 16;13:1109019. doi: 10.3389/fneur.2022.1109019. eCollection 2022.
Screening for metabolically relevant differentially expressed genes (DEGs) shared by hepatocellular carcinoma (HCC) and vascular cognitive impairment (VCI) to explore the possible mechanisms of HCC-induced VCI.
Based on metabolomic and gene expression data for HCC and VCI, 14 genes were identified as being associated with changes in HCC metabolites, and 71 genes were associated with changes in VCI metabolites. Multi-omics analysis was used to screen 360 DEGs associated with HCC metabolism and 63 DEGs associated with VCI metabolism.
According to the Cancer Genome Atlas (TCGA) database, 882 HCC-associated DEGs were identified and 343 VCI-associated DEGs were identified. Eight genes were found at the intersection of these two gene sets: NNMT, PHGDH, NR1I2, CYP2J2, PON1, APOC2, CCL2, and SOCS3. The HCC metabolomics prognostic model was constructed and proved to have a good prognostic effect. The HCC metabolomics prognostic model was constructed and proved to have a good prognostic effect. Following principal component analyses (PCA), functional enrichment analyses, immune function analyses, and TMB analyses, these eight DEGs were identified as possibly affecting HCC-induced VCI and the immune microenvironment. As well as gene expression and gene set enrichment analyses (GSEA), a potential drug screen was conducted to investigate the possible mechanisms involved in HCC-induced VCI. The drug screening revealed the potential clinical efficacy of A-443654, A-770041, AP-24534, BI-2536, BMS- 509744, CGP-60474, and CGP-082996.
HCC-associated metabolic DEGs may influence the development of VCI in HCC patients.
筛选肝细胞癌（HCC）和血管性认知障碍（VCI）共有的代谢相关差异表达基因（DEG），以探索HCC诱发VCI的可能机制。
基于HCC和VCI的代谢组学和基因表达数据，确定了14个与HCC代谢物变化相关的基因以及71个与VCI代谢物变化相关的基因。采用多组学分析筛选出360个与HCC代谢相关的DEG和63个与VCI代谢相关的DEG。
根据癌症基因组图谱（TCGA）数据库，确定了882个与HCC相关的DEG和343个与VCI相关的DEG。在这两个基因集的交集处发现了8个基因：NNMT、PHGDH、NR1I2、CYP2J2、PON1、APOC2、CCL2和SOCS3。构建了HCC代谢组学预后模型，并证明其具有良好的预后效果。经过主成分分析（PCA）、功能富集分析、免疫功能分析和肿瘤突变负荷（TMB）分析，确定这8个DEG可能影响HCC诱发的VCI和免疫微环境。通过基因表达和基因集富集分析（GSEA），进行了潜在药物筛选，以研究HCC诱发VCI的可能机制。药物筛选揭示了A-443654、A-770041、AP-24534、BI-2536、BMS-509744、CGP-60474和CGP-082996的潜在临床疗效。
与HCC相关的代谢DEG可能影响HCC患者VCI的发生发展。
