Zhang Dong, Xiang Kai-Fang, Hong Chen-Chen, Bao Xiao-Ping, Wu Yan, Wu Rui
Department of General Surgery, Kong Jiang Hosptal, Shanghai, China.
Department of Thyroid and Breast Surgery, Geriatric Hospital Affiliated with Wuhan University of Science and Technology, Wuhan, Hubei, China.
Front Genet. 2025 Jul 30;16:1593553. doi: 10.3389/fgene.2025.1593553. eCollection 2025.
Papillary thyroid carcinoma (PTC) has a lymph node metastasis rate of 20%-90%. This study aims to explore the role and regulatory mechanism of the FAM27E3 in PTC lymph node metastasis.
The seven thyroid cancer (THCA) datasets from the Gene Expression Omnibus (GEO) were combined as the training group, while the PTC dataset served as the testing group. Venn analysis identified overlapping genes through consistent cluster analysis and weighted gene co-expression network analysis (WGCNA). We used the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases to perform gene set enrichment analysis (GSEA) to explore the enriched terms. Least absolute shrinkage and selection operator (LASSO) analysis was applied to the overlapping genes to identify key influence factors. Finally, FAM27E3 was used for score analysis (epithelial-mesenchymal transition (EMT), angiogenesis, and mRNAsi scores). Immune cell infiltration was assessed using the CIBERSORT algorithm. CCK8, colony formation, Transwell assays, Western blotting, and RT-PCR were employed to evaluate cell viability, invasion, migration, and gene/protein expression.
The clustering method distinguished the samples into two subtypes. We obtained the mRNA expression levels of 128 overlapping genes from the tumor and C1 modules of the GSE60542 dataset. FAM27E3 was identified as a hub gene associated with PTC lymph node metastasis and had a significantly positive correlation with EMT_score. The MRNAsi_score was increased in the FAM27E3 high-expression group. A high expression of FAM27E3 indicated a reduction in the overall macrophage levels. FAM27E3 exhibited high expression in PTC cell lines, and its downregulation suppressed cell proliferation, migration, and invasion. FAM27E3 promoted the lymph node metastasis of PTC, which was associated with the p53 signaling pathway.
FAM27E3, as a marker for PTC lymph node metastasis, promotes PTC lymph node metastasis related to the p53 signaling pathway.
甲状腺乳头状癌（PTC）的淋巴结转移率为20%-90%。本研究旨在探讨FAM27E3在PTC淋巴结转移中的作用及调控机制。
将来自基因表达综合数据库（GEO）的7个甲状腺癌（THCA）数据集合并作为训练组，而PTC数据集作为测试组。通过一致性聚类分析和加权基因共表达网络分析（WGCNA）进行Venn分析以鉴定重叠基因。我们使用基因本体论（GO）和京都基因与基因组百科全书（KEGG）数据库进行基因集富集分析（GSEA）以探索富集术语。将最小绝对收缩和选择算子（LASSO）分析应用于重叠基因以鉴定关键影响因素。最后，对FAM27E3进行评分分析（上皮-间质转化（EMT）、血管生成和mRNAsi评分）。使用CIBERSORT算法评估免疫细胞浸润。采用CCK8、集落形成、Transwell实验、蛋白质免疫印迹法和逆转录-聚合酶链反应来评估细胞活力、侵袭、迁移以及基因/蛋白质表达。
聚类方法将样本分为两个亚型。我们从GSE60542数据集的肿瘤和C1模块中获得了128个重叠基因的mRNA表达水平。FAM27E3被鉴定为与PTC淋巴结转移相关的枢纽基因，并且与EMT_score显著正相关。FAM27E3高表达组的MRNAsi_score升高。FAM27E3的高表达表明总体巨噬细胞水平降低。FAM27E3在PTC细胞系中高表达，其下调抑制细胞增殖、迁移和侵袭。FAM27E3促进PTC的淋巴结转移，这与p53信号通路相关。
FAM27E3作为PTC淋巴结转移的标志物，促进与p53信号通路相关的PTC淋巴结转移。
