将 FADS3 作为头颈部鳞状细胞癌预后和免疫标志物的综合分析。

IF 4.4 2区生物学 Q2 CELL BIOLOGY

Cellular signalling Pub Date : 2024-09-27 DOI:10.1016/j.cellsig.2024.111437

Haonan Tang , Yanlin Geng , Keyi Wang , Yuchi Zhu , Yuan Fan , Yanting Wang

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引用次数: 0

摘要

背景：长链多不饱和脂肪酸的形成需要脂肪酸去饱和酶（FADS），而脂肪酸去饱和酶与癌症进展密切相关。方法：从 TCGA 和 GEO 数据库中检索 HNSCC 病例，鉴定具有转录差异表达的 FADS 成员。同时还研究了HNSCC的临床生存率、肿瘤微环境（TME）和潜在致病机制。这些结果通过组织染色、流式细胞术和 HNSCC 细胞系的功能研究得到了验证：结果：HNSCC与正常上皮组织相比，前者的FADS3表达量更高。FADS3 的上调与不良临床预后相关。FADS3是HNSCC患者总生存率低的独立预后因素。KEGG、GO和GSEA显示，FADS3的表达与多个免疫相关通路和上皮-间质转化（EMT）相关。敲除FADS3可抑制HNSCC细胞的增殖、迁移、侵袭和EMT。单细胞数据集分析表明了FADS3与TME特征之间的关联。进一步研究发现，FADS3 高的肿瘤原位组织和外周血中 CD8+ T 细胞较少。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HNSCC进展过程中调控FADS3表达的CYTOR/hsa-let-7c-5p轴：结论：FADS3可能是HNSCC的治疗靶点，它与HNSCC的预后、EMT、免疫浸润和ceRNA调控网络有关。

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Integrative analysis of FADS3 as a marker for prognosis and immunity in head and neck squamous cell carcinoma

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^high 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.

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来源期刊

Cellular signalling 生物-细胞生物学

CiteScore

8.40

自引率

0.00%

发文量

250

审稿时长

27 days

期刊介绍： Cellular Signalling publishes original research describing fundamental and clinical findings on the mechanisms, actions and structural components of cellular signalling systems in vitro and in vivo. Cellular Signalling aims at full length research papers defining signalling systems ranging from microorganisms to cells, tissues and higher organisms.