基于多数据库分析FMO1在胃癌中的表达、临床意义及生物学功能

The FMO1 Expression, Clinical Significance and Biological Functions in Gastric Cancer Based on Multi-Database Analysis

摘要: 目的：探讨FMO1基因在胃癌组织中的表达特征、与临床病理参数的关系，分析其与肿瘤进展相关信号通路、肿瘤微环境的关联，评估其作为胃癌潜在的预后标志物和有待进一步研究的治疗靶点的价值。方法：采用生物信息学方法分析FMO1在胃癌中的表达及其与患者生存的关系。运用GSEA、GO、KEGG富集分析解析FMO1相关的功能通路。使用ESTIMATE算法和ssGSEA进行免疫浸润分析。结果：在TCGA和GEO数据库中，FMO1在肿瘤组织中的表达均显著高于正常组织。与T1、Stage I、G1~G2分级的胃癌患者相比，T2~T4、Stage II~IV、G3分级胃癌组织中FMO1表达水平显著升高。Kaplan-Meier生存分析显示，FMO1高表达组患者的总生存期和疾病特异性生存期均显著短于低表达组。多因素Cox回归分析显示FMO1高表达是胃癌患者不良预后的独立风险因素。ESTIMATE算法显示，FMO1高表达组的基质评分、免疫评分及ESTIMATE评分均显著更高。免疫细胞浸润分析表明，FMO1表达与巨噬细胞、调节性T细胞的浸润丰度呈正相关。GO、KEGG富集分析显示，FMO1共表达基因富集于细胞外基质组织、PI3K-Akt、Wnt等肿瘤相关通路。GSEA进一步证实，FMO1高表达与ECM-受体相互作用、PD-1/CTLA-4免疫检查点以及PI3K-Akt、JAK-STAT和MAPK等信号通路的激活状态呈正相关。结论：FMO1基因在胃癌中高表达，与临床病理特征及患者预后相关。FMO1可能参与基质重塑、免疫抑制的多维调控网络，参与胃癌恶性进展，凸显了其作为胃癌潜在的预后标志物和有待进一步研究的治疗靶点的价值。

Abstract: Objective: To investigate the expression characteristics of the flavin-containing monooxygenase 1 (FMO1) gene in gastric cancer (GC) tissues, its association with clinicopathological parameters, and its correlation with tumor‑progress‑related signaling pathways and tumor microenvironment, so as to evaluate its value as a potential prognostic biomarker and a therapeutic target to be further studied for GC. Methods: Bioinformatics methods were employed to analyze FMO1 expression in GC and its relationship with patient survival. Gene Set Enrichment Analysis (GSEA), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were utilized to elucidate FMO1-associated functional pathways. Immune cell infiltration was assessed using the ESTIMATE algorithm and single-sample GSEA (ssGSEA). Results: In both The Cancer Genome Atlas and Gene Expression Omnibus databases, FMO1 expression was significantly higher in tumor tissues compared to adjacent normal tissues. Compared to patients with T1 stage, Stage I, or G1~G2 grade, FMO1 expression levels were significantly elevated in GC tissues from patients with T2~T4 stages, Stage II~IV, or G3 grade. Kaplan-Meier survival analysis revealed that patients with high FMO1 expression had significantly shorter overall survival and disease-specific survival than those with low expression. Multivariate Cox regression analysis identified high FMO1 expression as an independent risk factor for poor prognosis in GC patients. The ESTIMATE algorithm showed significantly higher stromal, immune, and ESTIMATE scores in the high FMO1 expression group. Immune cell infiltration analysis indicated a positive correlation between FMO1 expression and the infiltration abundance of macrophages and regulatory T cells. GO and KEGG enrichment analyses demonstrated that FMO1-co-expressed genes were enriched in tumor-related pathways such as extracellular matrix organization, PI3K-Akt signaling, and Wnt signaling. GSEA further confirmed that high FMO1 expression was positively correlated with the activation status of ECM‑receptor interaction, PD‑1/CTLA‑4 immune checkpoints, as well as PI3K‑Akt, JAK‑STAT and MAPK signaling pathways. Conclusion: The FMO1 gene is highly expressed in GC and is associated with clinicopathological features and patient prognosis. FMO1 may participate in the multi‑dimensional regulatory network of stromal remodeling and immunosuppression to facilitate malignant progression of gastric cancer, highlighting its value as a potential prognostic biomarker and a therapeutic target to be further studied for gastric cancer.