■成纤维细胞激活蛋白(FAP),一种细胞表面丝氨酸蛋白酶,参与肿瘤的侵袭和免疫调节。然而,目前尚无FAP的泛癌症分析。目的:我们旨在评估FAP的泛癌表达谱,它的分子功能,及其在头颈部鳞状细胞癌(HNSC)中的潜在作用。
■我们分析了基因表达,生存状态,免疫浸润,和FAP在癌症基因组图谱(TCGA)和基因型组织表达(GTEx)肿瘤中的分子功能通路。此外,为了阐明FAP在HNSC中的作用,我们进行了增殖,迁移,和FAP过表达或敲低后的侵袭测定。
■FAP表达在9种肿瘤类型中升高,并且与其中8种肿瘤的低生存率相关。在免疫浸润的背景下,在五种肿瘤类型中,FAP表达与CD8T细胞浸润呈负相关,而在四种肿瘤类型中,FAP表达与调节性T细胞浸润呈正相关。我们的富集分析强调了FAP参与PI3K-Akt信号通路。在HNSC细胞中,FAP过表达激活PI3K-Akt通路,促进肿瘤增殖,迁移,和入侵。相反,FAP敲低显示出抑制作用。
■我们的研究揭示了FAP与多种癌症的不良肿瘤预后的关联,并强调了其作为HNSC治疗靶点的潜力。
UNASSIGNED: Fibroblast activation protein (
FAP), a cell surface serine protease, plays roles in tumor invasion and immune regulation. However, there is currently no pan-cancer analysis of
FAP. Objective: We aimed to assess the pan-cancer expression profile of FAP, its molecular function, and its potential role in head and neck squamous cell carcinoma (HNSC).
UNASSIGNED: We analyzed gene expression, survival status, immune infiltration, and molecular functional pathways of FAP in The Cancer Genome Atlas (TCGA) and Genotype Tissue Expression (GTEx) tumors. Furthermore, to elucidate the role of FAP in HNSC, we performed proliferation, migration, and invasion assays post-
FAP overexpression or knock-down.
UNASSIGNED: FAP expression was elevated in nine tumor types and was associated with poor survival in eight of them. In the context of immune infiltration, FAP expression negatively correlated with CD8+ T-cell infiltration in five tumor types and positively with regulatory T-cell infiltration in four tumor types. Our enrichment analysis highlighted
FAP\'s involvement in the PI3K-Akt signaling pathway. In HNSC cells, FAP overexpression activated the PI3K-Akt pathway, promoting tumor proliferation, migration, and invasion. Conversely,
FAP knockdown showed inhibitory effects.
UNASSIGNED: Our study unveils the association of FAP with poor tumor prognosis across multiple cancers and highlights its potential as a therapeutic target in HNSC.