Jiang Xiaohua, Chen Liqi, Xu Zixia, Sun Hangzhe, Ye Jing, Guo Ziyi, Xiao Mang
Department of Otolaryngology Head and Neck Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Zhejiang, 310016, China.
The Second School of Clinical Medicine, Wenzhou Medical University, Wenzhou, 325035, China.
Discov Oncol. 2025 Aug 8;16(1):1509. doi: 10.1007/s12672-025-03372-8.
Head and Neck Squamous Cell Carcinoma (HNSCC) is a prevalent and deadly cancer with limited treatment options, for which autophagy has a dual impact. Nitazoxanide is a broad-spectrum antiviral drug showing promise in treating cancer, but its role in regulating autophagy in HNSCC remains unexplored.
The molecular mechanisms were explored through Differential expression analysis, functional enrichment analysis, risk prognostic model, nomogram model, GSEA, GSVA, WGCNA, mutation analysis, scRNA analysis, spatial transcriptomic analysis, and L1000FWD analysis. And the impact of Nitazoxanide was experimentally verified.
We identified 32 differentially expressed ARGs and 4 hub genes. They are involved in autophagy, apoptosis, and human cytomegalovirus infection. And hub genes were identified as independent prognostic factors for HNSCC. GSEA, GSVA and WGCNA uncovered the role of the dysregulation of IFN-α response pathway in HNSCC. scRNA and spatial transcriptomic analyses revealed the expression models of each hub gene. Furthermore, potential drugs were explored using L1000FWD analysis. Additionally, Nitazoxanide's function was verified in vitro.
Our findings established that Nitazoxanide has the potential to play a role in the treatment of HNSCC. We suggested that Nitazoxanide acts on NKX2-3, PINK1, BIRC5 and CDKN2A to inhibit the development of HNSCC through regulating autophagy, and it is a promising candidate drug for HNSCC.
头颈部鳞状细胞癌（HNSCC）是一种常见且致命的癌症，治疗选择有限，自噬在其中具有双重影响。硝唑尼特是一种广谱抗病毒药物，在癌症治疗方面显示出前景，但其在调节HNSCC自噬中的作用仍未得到探索。
通过差异表达分析、功能富集分析、风险预后模型、列线图模型、基因集富集分析（GSEA）、基因集变异分析（GSVA）、加权基因共表达网络分析（WGCNA）、突变分析、单细胞RNA分析、空间转录组分析和L1000FWD分析来探索分子机制。并通过实验验证了硝唑尼特的影响。
我们鉴定出32个差异表达的自噬相关基因（ARGs）和4个枢纽基因。它们参与自噬、凋亡和人巨细胞病毒感染。并且枢纽基因被确定为HNSCC的独立预后因素。GSEA、GSVA和WGCNA揭示了IFN-α反应通路失调在HNSCC中的作用。单细胞RNA和空间转录组分析揭示了每个枢纽基因的表达模式。此外，使用L1000FWD分析探索了潜在药物。此外，在体外验证了硝唑尼特的功能。
我们的研究结果表明硝唑尼特在HNSCC治疗中具有发挥作用的潜力。我们认为硝唑尼特作用于NKX2-3、PINK1、BIRC5和CDKN2A，通过调节自噬来抑制HNSCC的发展，它是HNSCC一种有前景的候选药物。
