Cui Kun, Tang Shifu, Wei Jing, Wang Wanping, Deng Yaoming
Department of Laboratory Medicine, Liuzhou People's Hospital, Liu Zhou, 545006, China.
Liuzhou Key Laboratory of Precision Medicine for Viral Diseases, Liu Zhou, China.
Biochem Biophys Rep. 2025 May 15;42:102046. doi: 10.1016/j.bbrep.2025.102046. eCollection 2025 Jun.
Head and neck squamous cell carcinoma (HNSC) is the sixth most prevalent cancer worldwide, with approximately 700,000 new cases each year. Due to its heterogeneity, reliable biomarkers are crucial for guiding treatment. Fibroblast activation protein (FAP) has been implicated in HNSC progression, but its specific involvement in ferroptosis and the ceRNA network is still not well understood. In this study, data from The Cancer Genome Atlas (TCGA) HNSC dataset were analyzed to examine the relationship between FAP expression and drug sensitivity, clinical features, methylation status, ferroptosis, immune infiltration, prognosis, and ceRNA networks. The results showed that FAP expression was significantly higher in HNSC tissues compared to normal tissues and was linked to increased sensitivity to 25 antitumor drugs, as well as poorer prognosis and unfavorable clinicopathological features. Lower methylation levels of FAP were also associated with higher mRNA expression and worse outcomes. Thirteen ferroptosis-related genes (FRGs) were identified, and four distinct ferroptosis clusters were characterized, with one cluster (C3) showing better survival rates. FAP was further linked to multiple immune cell types, immune markers, and key pathways such as PI3K-Akt and TGF-β. Additionally, a ceRNA network (NOP14-AS1/hsa-miRNA-30e-5p/FAP) was established, which correlated with overall survival in HNSC patients. These findings suggest that FAP may serve as a promising prognostic biomarker in HNSC, influencing both ferroptosis and the tumor microenvironment, providing potential targets for future therapies.
头颈部鳞状细胞癌（HNSC）是全球第六大常见癌症，每年新增病例约70万例。由于其异质性，可靠的生物标志物对于指导治疗至关重要。成纤维细胞活化蛋白（FAP）与HNSC进展有关，但其在铁死亡和竞争性内源性RNA（ceRNA）网络中的具体作用仍不清楚。本研究分析了来自癌症基因组图谱（TCGA）HNSC数据集的数据，以研究FAP表达与药物敏感性、临床特征、甲基化状态、铁死亡、免疫浸润、预后和ceRNA网络之间的关系。结果表明，与正常组织相比，HNSC组织中FAP表达显著更高，并且与对25种抗肿瘤药物的敏感性增加、预后较差和不良临床病理特征相关。FAP的低甲基化水平也与更高的mRNA表达和更差的结果相关。鉴定出13个铁死亡相关基因（FRGs），并对四个不同的铁死亡簇进行了特征描述，其中一个簇（C3）显示出更好的生存率。FAP还与多种免疫细胞类型、免疫标志物以及PI3K-Akt和TGF-β等关键通路相关。此外，建立了一个ceRNA网络（NOP14-AS1/hsa-miRNA-30e-5p/FAP），其与HNSC患者的总生存期相关。这些发现表明，FAP可能是HNSC中有前景的预后生物标志物，影响铁死亡和肿瘤微环境，为未来治疗提供潜在靶点。
