已在多种癌症类型中检测到 Forkhead Box N2 (FOXN2) 表达失调。然而，FOXN2 导致胃癌 (GC) 发生和进展的潜在机制在很大程度上仍未被探索。本研究旨在阐明FOXN2在GC中的潜在作用、其下游分子机制及其作为GC新型血清生物标志物的可行性。收集了GC患者和相应非癌组织的组织样本。外周血样本取自 GC 患者和健康对照。使用定量实时 PCR、蛋白质印迹和免疫组织化学测定 FOXN2 的表达。通过用小干扰 RNA (siRNA) 或 pcDNA 3.1 表达载体转染来调节 GC 细胞中 FOXN2 的表达。使用 Cell Counting Kit-8 和 5-乙炔基-2'-脱氧尿苷掺入测定法评估细胞增殖。通过Transwell实验评估细胞的迁移和侵袭能力，通过流式细胞仪测量细胞凋亡率，并通过蛋白质印迹分析评估增殖、凋亡和上皮间质转化（EMT）标志物的表达。在GC的血清、组织和细胞中过度表达，与远处转移和TNM分期相关。 FOXN2 在区分 GC 患者和健康个体方面表现出诊断价值，FOXN2 水平越高表明生存率越差。体外沉默FOXN2可抑制GC细胞的增殖、侵袭、迁移和EMT，同时促进细胞凋亡。 FOXN2 显示通过与分区缺陷 6 同源α (PARD6A) 的相互作用来调节 GC 细胞中的转化生长因子-β (TGFβ) 受体信号通路。 总之，我们的数据表明 FOXN2 作为 GC 中的致癌因子，调节通过与 PARD6A 结合来影响 TGFβ 通路，从而影响胃癌的发生。这项研究强调了 FOXN2 作为 GC 潜在血清生物标志物和治疗靶点的功能意义。

Dysregulated expression of Forkhead Box N2 (FOXN2) has been detected in various cancer types. However, the underlying mechanisms by which FOXN2 contributes to the onset and progression of gastric cancer (GC) remain largely unexplored. This study aimed to elucidate the potential role of FOXN2 within GC, its downstream molecular mechanisms, and its feasibility as a novel serum biomarker for GC.Tissue samples from GC patients and corresponding non-cancerous tissues were collected. Peripheral blood samples were obtained from GC patients and healthy controls. The expression of FOXN2 was determined using quantitative real-time PCR, western blotting, and immunohistochemistry. The expression of FOXN2 in GC cells was modulated by transfection with small interfering RNA (siRNA) or the pcDNA 3.1 expression vector. Cell proliferation was assessed using the Cell Counting Kit-8 and 5-ethynyl-2'-deoxyuridine incorporation assays. The migratory and invasive capacities of cells were evaluated by Transwell assays, apoptosis rates were measured by flow cytometry, and the expression of proliferative, apoptotic, and epithelial-mesenchymal transition (EMT) markers were assessed by western blot analysis.FOXN2 was found to be overexpressed in the serum, tissues, and cells of GC, correlating with distant metastasis and TNM staging. FOXN2 demonstrated diagnostic value in differentiating GC patients from healthy individuals, with higher levels of FOXN2 being indicative of poorer survival rates. Silencing FOXN2 in vitro inhibited the proliferation, invasion, migration, and EMT of GC cells, while promoting apoptosis. FOXN2 was shown to regulate the transforming growth factor-beta (TGFβ) receptor signaling pathway in GC cells via its interaction with Partitioning Defective 6 Homolog Alpha (PARD6A).In summary, our data suggest that FOXN2 acts as an oncogenic factor in GC, modulating the TGFβ pathway by binding to PARD6A, thereby influencing gastric carcinogenesis. This study underscores the functional significance of FOXN2 as a potential serum biomarker and therapeutic target in GC.