肿瘤细胞治疗研究
英文原题：Molecular Functions and Drug Prediction of MMP1 and TGFBR2 in Nasopharyngeal Carcinoma.
MMP1和TGFBR2被确定为EMT相关生物标志物，在NPC中介导免疫逃逸和转移。地塞米松可能靶向这些基因，为NPC提供一种新的治疗策略。
鼻咽癌（NPC）部分由上皮-间质转化（EMT）驱动。我们通过计算和机器学习方法，识别了NPC潜在的EMT相关生物标志物和靶向药物。
基于公共数据库来源的鼻咽癌患者数据集，使用limma包筛选差异表达基因（DEGs），并与上皮-间充质转化相关基因数据库（dbEMT）中的EMT基因集取交集。随后进行GO和KEGG富集分析，并通过STRING数据库构建蛋白-蛋白相互作用（PPI）网络。通过LASSO回归和SVM-RFE算法鉴定核心基因。使用CIBERSORT评估免疫细胞浸润；使用GSEA软件分析通路富集；通过Enrichr预测靶向药物；并使用AutoDock进行分子对接验证。最后，利用鼻咽癌细胞系对所选基因进行功能验证。
在131个EMT基因中，通过PPI筛选出18个。机器学习算法结合外部数据集验证进一步确定MMP1和TGFBR2为核心基因。MMP1与M0/M1巨噬细胞和活化NK细胞相关，而TGFBR2与静息NK细胞和记忆B细胞相关。这两个基因均与EMT、血管生成、缺氧和MYC靶点相关。地塞米松对MMP1（-7.72 kcal/mol）和TGFBR2（-7.27 kcal/mol）显示出强结合亲和力。细胞实验显示NPC细胞中MMP1上调、TGFBR2下调；MMP1敲低抑制了NPC恶性表型。
BACKGROUND: Nasopharyngeal carcinoma (NPC) is partially driven by epithelial-mesenchymal transition (EMT). We identified potential EMT-related biomarkers and targeted drugs for NPC via computational and machine learning approaches. METHODS: Based on the NPC patient dataset derived from the public database, differentially expressed genes (DEGs) were screened using the limma package and intersected with the EMT gene set from the database of Epithelial-Mesenchymal Transition-associated genes (dbEMT). Subsequently, GO and KEGG enrichment analyses were performed, and a protein-protein interaction (PPI) network was constructed via the STRING database. Core genes were identified through LASSO regression and SVM-RFE algorithms. Immune cell infiltration was assessed using CIBERSORT; pathway enrichment was analyzed with GSEA software; targeted drugs were predicted via Enrichr; and molecular docking validation was performed using AutoDock. Finally, the selected genes were functionally validated using NPC cell lines. RESULTS: Among 131 EMT genes, 18 were filtered via PPI. Machine learning algorithms combined with external dataset validation further pinpointed MMP1 and TGFBR2 as hub genes. MMP1 was correlated with M0/M1 macrophages and activated NK cells, whereas TGFBR2 was correlated with resting NK cells and memory B cells. Both genes were linked to EMT, angiogenesis, hypoxia, and MYC targets. Dexamethasone showed strong binding affinity to MMP1 (-7.72 kcal/mol) and TGFBR2 (-7.27 kcal/mol). Cellular assays revealed upregulated MMP1 and downregulated TGFBR2 in NPC cells; MMP1 knockdown suppressed NPC malignant phenotypes. CONCLUSION: MMP1 and TGFBR2 were identified as EMT-related biomarkers that mediated immune evasion and metastasis in NPC. Dexamethasone may target these genes, offering a novel therapeutic strategy for NPC.
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