Tianjin Medical University, Tianjin, China.
Tianjin Children's Hospital, Tianjin, China.
Biochem Genet. 2024 Aug;62(4):2743-2765. doi: 10.1007/s10528-023-10566-8. Epub 2023 Nov 27.
This study aims to identify the key genes and their regulatory networks by bioinformatics, increasing understanding of childhood obesity. The data comes from the GEO and Immport database. The immune microenvironment was explored in GSE104815. Key genes were identified by intersection of DEGs with the immune gene set. Enrichment analysis revealed gene-related functions and correlation analysis explored the relationship. Regulatory networks were constructed based on miRcode, TarBase and TargetScan databases. GSE29718 was used to validate our findings. Intercellular communication and cell differentiation trends were further explored using single-cell data from GSE153643. Based on our research, the immune microenvironment in the obese group showed higher immune infiltration. We found 962 DEGs and CXCL2 was identified as the key gene. The co-regulatory network of lncRNA-miRNA-mRNA suggested that obtaining TM4SF19-AS1, GUSBP11, AC105020.1, LINC00189, COL4A2-AS2, VIPR1-AS1 and LINC00242 may regulate CXCL2 (r > 0.9 and P < 0.01). Differential expression of CXCL2 was validated in GSE29718 (P < 0.05) and CXCL2 was identified as a biomarker for childhood obesity (AUC = 0.885). GSVA enrichment analysis revealed many pathways of high group obtaining the TNF-α signaling via NF-κB pathway and interferon γ response pathway. In GSE153643, 11 cell types were identified and CXCL2 was highly expressed in monocyte, macrophage, endothelial cell and pericyte. In CXCL2 high expressing macrophages, there was a tendency for cells to polarize toward M1 macrophages (P < 0.05). In summary, we identified CXCL2 as a potential biomarker of childhood obesity. The development of childhood obesity may be associated with the activation of immune infiltration of macrophage M1 polarization by CXCL2 expression.
本研究旨在通过生物信息学方法鉴定关键基因及其调控网络，以增加对儿童肥胖的理解。数据来自 GEO 和 Immport 数据库。在 GSE104815 中探索了免疫微环境。通过与免疫基因集的交集鉴定关键基因。富集分析揭示了与基因相关的功能，相关分析探索了基因之间的关系。基于 miRcode、TarBase 和 TargetScan 数据库构建了调控网络。使用 GSE29718 验证了我们的发现。使用 GSE153643 的单细胞数据进一步探索了细胞间通讯和细胞分化趋势。基于我们的研究，肥胖组的免疫微环境显示出更高的免疫浸润。我们发现了 962 个差异表达基因，其中 CXCL2 被鉴定为关键基因。lncRNA-miRNA-mRNA 的共调控网络提示，获得 TM4SF19-AS1、GUSBP11、AC105020.1、LINC00189、COL4A2-AS2、VIPR1-AS1 和 LINC00242 可能调节 CXCL2（r>0.9，P<0.01）。在 GSE29718 中验证了 CXCL2 的差异表达（P<0.05），并将 CXCL2 鉴定为儿童肥胖的生物标志物（AUC=0.885）。GSVA 富集分析显示，高表达组通过 NF-κB 通路和干扰素 γ 反应通路获得了许多 TNF-α 信号通路。在 GSE153643 中，鉴定了 11 种细胞类型，并且 CXCL2 在单核细胞、巨噬细胞、内皮细胞和周细胞中高度表达。在 CXCL2 高表达的巨噬细胞中，细胞向 M1 巨噬细胞极化的趋势（P<0.05）。总之，我们鉴定出 CXCL2 可能是儿童肥胖的潜在生物标志物。儿童肥胖的发展可能与 CXCL2 表达激活巨噬细胞 M1 极化的免疫浸润有关。
