陆军军医大学第二附属医院临床医学研究中心,重庆 400037
Received:30 August 2024,
Published:25 June 2025
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毛杨,王文静,李德峰.趋化因子CCL家族对甲状腺癌的影响及风险模型构建[J].局解手术学杂志,2025,34(06):494-500.
MAO Yang,WANG Wen-jing,LI De-feng.Effect of CCL chemokine family on thyroid carcinoma and the construction of a risk model[J].JOURNAL OF REGIONAL ANATOMY AND OPERATIVE SURGERY,2025,34(06):494-500.
毛杨,王文静,李德峰.趋化因子CCL家族对甲状腺癌的影响及风险模型构建[J].局解手术学杂志,2025,34(06):494-500. DOI: 10.11659/jjssx.08E024127.
MAO Yang,WANG Wen-jing,LI De-feng.Effect of CCL chemokine family on thyroid carcinoma and the construction of a risk model[J].JOURNAL OF REGIONAL ANATOMY AND OPERATIVE SURGERY,2025,34(06):494-500. DOI: 10.11659/jjssx.08E024127.
目的
2
通过分析TCGA-THCA数据集中的基因表达数据,识别甲状腺癌(THCA)相关的差异表达基因,构建风险模型并探讨趋化因子CCL家族在THCA进展中的作用及其对肿瘤免疫微环境的影响。
方法
2
下载并分析TCGA-THCA数据集,包含512个癌症样本和59个癌旁组织样本。通过差异分析R包取交集得到差异表达基因,并进行主成分分析(PCA)、基因本体(GO)及京都基因与基因组百科全书(KEGG)富集分析。使用CellMark、monocle和CellChat探索THCA的细胞图谱、细胞拟时序和细胞通讯。
结果
2
共发现698个上调基因和285个下调基因,PCA显示THCA组和正常组基因表达模式存在显著差异。GO及KEGG富集分析揭示,差异基因主要参与细胞外基质组织、细胞连接组装和补体系统等生物过程。风险模型评估结果显示,CCL基因与不良预后显著相关(
P
=0.005)。单细胞分析揭示成纤维细胞在THCA进展中的关键作用,CCL基因在成纤维细胞中表达显著上调(
P
<
0.05)。细胞拟时序结果显示CCL基因在细胞分化过程中差异表达;细胞通讯结果表明成纤维细胞与内皮细胞的相互作用在肿瘤微环境中至关重要。
结论
2
趋化因子CCL家族在THCA中的表达与不良预后密切相关,特别是CCL4通过与癌症相关成纤维细胞的CCR受体结合激活下游信号通路,进一步促进癌症发展,为理解趋化因子CCL家族在THCA中的作用及其调控肿瘤免疫微环境提供了新视角。
Objective
2
By analyzing the gene expression data in TCGA-THCA dataset, the differentially expressed genes related to thyroid carcinoma (THCA) were identified, a risk model was construct, and the role of CCL chemokine family in the development of THCA and its effect on the tumor immune microenvironment were investigated.
Methods
2
TCGA-THCA dataset was downloaded and analyzed, including 512 cancer samples and 59 adjacent tissue samples. The differentially expressed genes were obtained by taking the intersection of R packages of differential analysis, and the principal component analysis (PCA), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed. CellMarker, monocle, and CellChat were used to explore the Cell atlas, pseudotemporal trajectory, and cellular communication.
Results
2
A total of 698 up-regulated genes and 285 down-regulated genes were identified. PCA showed that there were significant differences in gene expression patterns between the THCA group and the normal group. GO and KEGG enrichment analysis reveal
ed that differentially expressed genes were mainly involved in biological processes such as extracellular matrix tissue, cell junction assembly, and complement system. The results of risk model showed that the CCL genes was significantly correlated with poor prognosis (
P
=0.005). Single cell analysis revealed that fibroblasts played a key role in the development of THCA, and the expression of CCL gene was significantly up-regulated in fibroblasts (
P
<
0.05). The results of pseudotemporal trajectory analysis showed that CCL gene was differentially expressed during cellular differentiation; the results of cellular communication analysis showed that the interaction between fibroblasts and endothelial cells is crucial in the tumor microenvironment.
Conclusion
2
The expression of CCL chemokine family in THCA is closely related to poor prognosis, especially CCL4, which activates the downstream signaling pathways by interacts with CCR receptors of cancer-associated fibroblasts, thereby promoting the development of cancer. These findings provide novel insights for understanding the role of CCL chemokine family in THCA and its regulation of the tumor immune microenvironment.
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