关键词: CCL11 HLF HNSCC Sensitive drugs Tumor stemness

Mesh : Humans Squamous Cell Carcinoma of Head and Neck / immunology genetics drug therapy pathology Neoplastic Stem Cells / metabolism pathology immunology drug effects Prognosis Head and Neck Neoplasms / genetics drug therapy immunology pathology Gene Expression Regulation, Neoplastic / drug effects Biomarkers, Tumor / genetics metabolism Gene Regulatory Networks Gene Expression Profiling Antineoplastic Agents / therapeutic use pharmacology

来  源:   DOI:10.1038/s41598-024-66196-6   PDF(Pubmed)

Abstract:
The presence of cancer stem cells (CSCs) contributes significantly to treatment resistance in various cancers, including head and neck squamous cell carcinoma (HNSCC). Despite this, the relationship between cancer stemness and immunity remains poorly understood. In this study, we aimed to identify potential immunotherapeutic targets and sensitive drugs for CSCs in HNSCC. Using data from public databases, we analyzed expression patterns and prognostic values in HNSCC. The stemness index was calculated using the single-sample gene set enrichment analysis (ssgsea) algorithm, and weighted gene co-expression network analysis (WGCNA) was employed to screen for key stemness-related modules. Consensus clustering was then used to group samples for further analysis, and prognosis-related key genes were identified through regression analysis. Our results showed that tumor samples from HNSCC exhibited higher stemness indices compared to normal samples. WGCNA identified a module highly correlated with stemness, comprising 187 genes, which were significantly enriched in protein digestion and absorption pathways. Furthermore, we identified sensitive drugs targeting prognostic genes associated with tumor stemness. Notably, two genes, HLF and CCL11, were found to be highly associated with both stemness and immunity. In conclusion, our study identifies a stemness-related gene signature and promising drug candidates for CSCs of HNSCC. Additionally, HLF and CCL11, which are associated with both stemness and immunity, represent potential targets for immunotherapy in HNSCC.
摘要:
癌症干细胞(CSC)的存在对各种癌症的治疗耐药性做出了重要贡献。包括头颈部鳞状细胞癌(HNSCC)。尽管如此,癌症干性和免疫力之间的关系仍然知之甚少。在这项研究中,我们旨在确定HNSCC中CSC的潜在免疫治疗靶点和敏感药物。使用来自公共数据库的数据,我们分析了HNSCC的表达模式和预后价值。利用单样本基因集富集分析(ssgsea)算法计算干性指数,采用加权基因共表达网络分析(WGCNA)筛选关键的干性相关模块。然后使用一致性聚类对样本进行分组以进行进一步分析,并通过回归分析确定与预后相关的关键基因。我们的结果表明,与正常样品相比,来自HNSCC的肿瘤样品表现出更高的干性指数。WGCNA确定了一个与干性高度相关的模块,包含187个基因,显著富集了蛋白质的消化和吸收途径。此外,我们确定了靶向与肿瘤干性相关的预后基因的敏感药物.值得注意的是,两个基因,发现HLF和CCL11与干性和免疫力高度相关。总之,我们的研究为HNSCC的CSC确定了与干性相关的基因标签和有希望的候选药物。此外,HLF和CCL11与干性和免疫力有关,代表HNSCC免疫治疗的潜在靶标。
公众号