FADS3 作为头颈部鳞状细胞癌预后和免疫标志物的综合分析。
Integrative analysis of FADS3 as a marker for prognosis and immunity in head and neck squamous cell carcinoma.
机构信息
Department of Oral Mucosal Diseases, The Affiliated Stomatological Hospital of Nanjing Medical University, China; State Key Laboratory Cultivation Base of Research, Prevention and Treatment for Oral Diseases, China; Jiangsu Province Engineering Research Center of Stomatological Translational Medicine, China.
Department of Oral Mucosal Diseases, The Affiliated Stomatological Hospital of Nanjing Medical University, China; State Key Laboratory Cultivation Base of Research, Prevention and Treatment for Oral Diseases, China; Jiangsu Province Engineering Research Center of Stomatological Translational Medicine, China.
出版信息
Cell Signal. 2024 Dec;124:111437. doi: 10.1016/j.cellsig.2024.111437. Epub 2024 Sep 27.
BACKGROUND
Long-chain polyunsaturated fatty acid formation requires fatty acid desaturase (FADS), which is strongly linked to cancer progression. Nevertheless, it's unclear how FADS3 functions in head and neck squamous cell carcinoma (HNSCC).
METHODS
HNSCC cases were retrieved from TCGA and GEO databases, and FADS members with transcriptionally differential expression were identified. Clinical survival, tumor microenvironment (TME), and potential pathogenic mechanism in HNSCC were also investigated. These results were validated using tissue staining, flow cytometry and functional studies in HNSCC cell lines.
RESULTS
When comparing HNSCC to normal epithelial tissues, FADS3 expression was much higher in the former. FADS3 upregulation was correlated with poor clinical outcomes. FADS3 was an independent prognostic factor for poor overall survival in HNSCC patients. KEGG, GO, and GSEA revealed that FADS3 expression correlated with several immune-related pathways and the epithelial-mesenchymal transition (EMT). Knocking down FADS3 restrained HNSCC cell proliferation, migration, invasion, and EMT. Single-cell dataset analysis showed an association between FADS3 and TME features. Further investigation revealed that FADS3 tumor was accompanied with less CD8 T cells in situ tissue and peripheral blood. FADS3 was positively correlated with immune-related molecules and could predict the adverse efficacy of immunotherapy. Finally, we constructed a CYTOR/hsa-let-7c-5p axis regulating FADS3 expression in HNSCC progression.
CONCLUSIONS
FADS3 may represent a target for treatment in HNSCC, which is linked to prognosis, EMT, immune infiltration, and ceRNA regulatory network of HNSCC.
背景
长链多不饱和脂肪酸的形成需要脂肪酸去饱和酶（FADS），而 FADS 与癌症的进展密切相关。然而，FADS3 在头颈部鳞状细胞癌（HNSCC）中的作用机制尚不清楚。
方法
从 TCGA 和 GEO 数据库中检索 HNSCC 病例，确定转录差异表达的 FADS 成员。还研究了 HNSCC 中的临床生存、肿瘤微环境（TME）和潜在的发病机制。这些结果通过组织染色、流式细胞术和 HNSCC 细胞系的功能研究进行了验证。
结果
与正常上皮组织相比，FADS3 在 HNSCC 中的表达明显更高。FADS3 的上调与不良的临床结局相关。FADS3 是 HNSCC 患者不良总生存期的独立预后因素。KEGG、GO 和 GSEA 表明，FADS3 表达与几种免疫相关途径和上皮-间充质转化（EMT）相关。敲低 FADS3 可抑制 HNSCC 细胞的增殖、迁移、侵袭和 EMT。单细胞数据集分析显示 FADS3 与 TME 特征之间存在关联。进一步研究表明，FADS3 肿瘤与原位组织和外周血中较少的 CD8 T 细胞有关。FADS3 与免疫相关分子呈正相关，可预测免疫治疗的不良疗效。最后，我们构建了一个 CYTOR/hsa-let-7c-5p 轴，调节 HNSCC 进展中的 FADS3 表达。
结论
FADS3 可能代表 HNSCC 治疗的一个靶点，与预后、EMT、免疫浸润和 HNSCC 的 ceRNA 调控网络有关。
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