Long Zhi-Qing, Ding Ran, Quan Ting-Qiu, Xu Rui, Huang Zhuo-Hui, Wei Denghui, Zheng Wei-Hong, Sun Ying
Department of Radiology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Guangzhou 510060, China.
Department of Radiation Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Guangzhou 510060, China.
Biomolecules. 2025 Feb 14;15(2):283. doi: 10.3390/biom15020283.
Aberrant expression and mutations in the fibroblast growth factor (FGF) family play crucial roles in cell differentiation, growth, and migration, contributing to tumor progression across various cancers. Nasopharyngeal carcinoma (NPC), a malignancy prevalent in East Asia, is primarily treated with radiotherapy; however, radioresistance remains a major challenge, leading to recurrence and poor outcomes. While FGFs are known to activate signaling pathways such as MAPK, PI3K/AKT, and JAK/STAT to promote cancer progression, the specific role of individual FGFs in NPC radioresistance remains unclear. Emerging evidence highlights as a key player in NPC progression, metastasis, and radioresistance, underscoring its potential as a therapeutic target to overcome treatment resistance and improve clinical outcomes.
We analyzed single nucleotide variation (SNV) data, gene expression, and DNA methylation patterns using cancer datasets, including TCGA and GTEx, to investigate expression. Differentially expressed genes (DEGs) were identified and interpreted using functional enrichment analysis, while survival analysis and gene set enrichment analysis (GSEA) were conducted to identify clinical correlations. DNA methylation patterns were specifically assessed using the HumanMethylation850 BeadChips on tissue samples from nine recurrent and nine non-recurrent NPC patients. Functional assays, including cell viability, migration, invasion, and clonogenic survival assays, were performed to evaluate the effects of FGF5 on NPC cell behavior in vitro and in vivo.
showed elevated SNV frequencies across multiple cancers, particularly in HNSC and NPC. DNA methylation analysis revealed an inverse relationship between expression and methylation levels in recurrent NPC tumors. Functional assays demonstrated that FGF5 enhances migration, invasion, and radioresistance in NPC cells. High FGF5 expression was associated with reduced distant metastasis-free survival (DMFS) and increased radioresistance, highlighting its role in metastatic progression and recurrence.
FGF5 plays a significant role in the progression and recurrence of nasopharyngeal carcinoma. Its elevated expression correlates with increased migration, invasion, and radioresistance as well as reduced distant metastasis-free survival. These findings suggest that FGF5 contributes to the metastatic and recurrence potential of NPC, making it a potential target for therapeutic intervention in treating these cancers.
成纤维细胞生长因子（FGF）家族的异常表达和突变在细胞分化、生长和迁移中起关键作用，促进了各种癌症的肿瘤进展。鼻咽癌（NPC）是东亚地区常见的恶性肿瘤，主要采用放射治疗；然而，放射抗性仍然是一个主要挑战，导致复发和不良预后。虽然已知FGF可激活丝裂原活化蛋白激酶（MAPK）、磷脂酰肌醇-3激酶/蛋白激酶B（PI3K/AKT）和Janus激酶/信号转导和转录激活因子（JAK/STAT）等信号通路以促进癌症进展，但单个FGF在NPC放射抗性中的具体作用仍不清楚。新出现的证据强调 作为NPC进展、转移和放射抗性的关键参与者，突出了其作为克服治疗抗性和改善临床结果的治疗靶点的潜力。
我们使用包括癌症基因组图谱（TCGA）和基因型-组织表达（GTEx）在内的癌症数据集分析单核苷酸变异（SNV）数据、基因表达和DNA甲基化模式，以研究 表达。使用功能富集分析鉴定和解释差异表达基因（DEG），同时进行生存分析和基因集富集分析（GSEA）以确定临床相关性。使用人类甲基化850K芯片对9例复发性和9例非复发性NPC患者的组织样本进行DNA甲基化模式的特异性评估。进行包括细胞活力、迁移、侵袭和克隆形成存活分析在内的功能测定，以评估FGF5对NPC细胞体外和体内行为的影响。
显示在多种癌症中，特别是在头颈部鳞状细胞癌（HNSC）和NPC中，SNV频率升高。DNA甲基化分析揭示了复发性NPC肿瘤中 表达与甲基化水平之间的负相关关系。功能测定表明，FGF5增强了NPC细胞的迁移、侵袭和放射抗性。高FGF5表达与无远处转移生存期（DMFS）降低和放射抗性增加相关，突出了其在转移进展和复发中的作用。
FGF5在鼻咽癌的进展和复发中起重要作用。其表达升高与迁移、侵袭和放射抗性增加以及无远处转移生存期降低相关。这些发现表明，FGF5促成了NPC的转移和复发潜力，使其成为治疗这些癌症的潜在治疗干预靶点。
