Li Dong, Bao Lihao, Liu Shaosheng, Ji Ke, Xu Xujiu, Yuan Jie, Xia Guihua
Department of Otolaryngology, Beilun District People's Hospital of Ningbo, Beilun District, No. 1288, Lushan East Road, Ningbo City, China.
Appl Biochem Biotechnol. 2025 Mar;197(3):2066-2092. doi: 10.1007/s12010-024-05130-y. Epub 2024 Dec 12.
Nasopharyngeal carcinoma (NPC) is a malignant tumor originating from nasopharyngeal mucosa. Anoikis, a form of programmed cell death induced by detachment from the extracellular matrix, normally prevents metastasis. Resistance to anoikis in cancer cells can enhance their metastatic potential. This study identifies anoikis-related genes (ARGs) associated with NPC to elucidate tumorigenesis mechanisms. Analysis of the GSE12452 dataset from GEO revealed 77 differentially expressed ARGs in NPC tissues. GO and KEGG analyses highlighted significant enrichment in apoptosis-related pathways. A PPI network identified MYC, FN1, BRCA1, and FGF2 as Hub genes. Correlation analysis showed MYC positively correlated with activated dendritic cells (p < 0.01) but negatively with naive CD4 T cells (p < 0.001). FN1 was positively correlated with activated dendritic cells (p < 0.01) and negatively with M1 macrophages (p < 0.05). FGF2 negatively correlated with naive CD4 T cells (p < 0.001), while BRCA1 was positively correlated with eosinophils (p < 0.01). GSVA and GSEA indicated that MYC, FN1, BRCA1, and FGF2 were significantly enriched in cell cycle and DNA replication pathways. Immunohistochemistry and qPCR of 50 NPC samples confirmed the overexpression of these genes. Knockdown of MYC, FN1, BRCA1, and FGF2 led to increased tumor cell malignancy, with statistical significance (p < 0.05). This study identifies MYC, FN1, BRCA1, and FGF2 as anoikis-related genes (ARGs) with significant regulatory roles in nasopharyngeal carcinoma (NPC). These ARGs are found to be involved in the development and progression of NPC, suggesting their potential as therapeutic targets for this cancer.
鼻咽癌(NPC)是一种起源于鼻咽黏膜的恶性肿瘤。失巢凋亡是一种由与细胞外基质脱离诱导的程序性细胞死亡形式,通常可防止转移。癌细胞对失巢凋亡的抗性可增强其转移潜能。本研究鉴定了与鼻咽癌相关的失巢凋亡相关基因(ARG),以阐明肿瘤发生机制。对来自基因表达综合数据库(GEO)的GSE12452数据集的分析显示,鼻咽癌组织中有77个差异表达的ARG。基因本体(GO)和京都基因与基因组百科全书(KEGG)分析突出了凋亡相关通路的显著富集。蛋白质-蛋白质相互作用(PPI)网络确定MYC、纤连蛋白1(FN1)、乳腺癌1号基因(BRCA1)和碱性成纤维细胞生长因子2(FGF2)为枢纽基因。相关性分析表明,MYC与活化树突状细胞呈正相关(p<0.01),但与初始CD4 T细胞呈负相关(p<0.001)。FN1与活化树突状细胞呈正相关(p<0.01),与M1巨噬细胞呈负相关(p<0.05)。FGF2与初始CD4 T细胞呈负相关(p<0.001),而BRCA1与嗜酸性粒细胞呈正相关(p<0.01)。基因集变异分析(GSVA)和基因集富集分析(GSEA)表明,MYC、FN1、BRCA1和FGF2在细胞周期和DNA复制通路中显著富集。对50例鼻咽癌样本的免疫组织化学和定量聚合酶链反应(qPCR)证实了这些基因的过表达。敲低MYC、FN1、BRCA1和FGF2导致肿瘤细胞恶性程度增加,具有统计学意义(p<0.05)。本研究确定MYC、FN1、BRCA1和FGF2为失巢凋亡相关基因(ARG),在鼻咽癌(NPC)中具有重要的调节作用。发现这些ARG参与鼻咽癌的发生和发展,表明它们作为该癌症治疗靶点的潜力。