血管生成与肿瘤微环境重塑和免疫治疗反应显著相关。我们的研究旨在构建胃癌的预后血管生成相关模型。使用公共数据库,血管生成相关的五基因(FGF1,GRB14,PAK3,PDGFRA,和PRKD1)进行了鉴定。前25%的患者被定义为高风险,其余为低风险。1-的曲线下面积,3-,5年总生存率(OS)分别为0.646,0.711和0.793.生存分析显示,低风险患者在构建(HR=0.57,p=0.002)和验证队列中有更好的10年OS。GO和GSEA揭示了DEGs在细胞外基质受体相互作用中的富集,树突状细胞抗原加工/呈递调节,和血管生成途径。CIBERSORT分析显示丰富的原始B细胞,静息的肥大细胞,静息CD4+记忆T细胞,M2巨噬细胞,和单核细胞在高风险亚组。TIMER数据库显示PAK3,FGF1,PRKD1和PDGFRA表达水平与CD4T细胞和巨噬细胞浸润之间存在强正相关。IOBR分析显示,高危亚组存在免疫抑制环境。低风险患者对抗PD1治疗的反应率较高。TMA显示FGF1过表达与不良预后及CD4+T细胞和巨噬细胞浸润有关。基于615小鼠的体内研究表明,抑制FGF1功能可以抑制肿瘤生长并增强抗PD1治疗功效。总之,我们建立了5项血管生成相关基因模型来预测胃癌患者的生存结局和免疫治疗反应,并将FGF1确定为改善免疫治疗的预后基因和潜在靶点.
Angiogenesis significantly correlates with tumor microenvironment remodeling and immunotherapy response. Our study aimed to construct a prognostic angiogenesis-related model for gastric cancer. Using public database, a angiogenetic related five-gene (
FGF1, GRB14, PAK3, PDGFRA, and PRKD1) model was identified. The top 25 % of patients were defined as high-risk, and the remaining as low-risk. The area under the curve for 1-, 3-, and 5-year overall survival (OS) were 0.646, 0.711, and 0.793, respectively. Survival analysis showed a better 10-year OS in low-risk patients in the construction (HR = 0.57, p = 0.002) and validation cohorts. GO and GSEA revealed that DEGs were enriched in extracellular matrix receptor interactions, dendritic cell antigen processing/presentation regulation, and angiogenesis pathways. CIBERSORT analysis revealed abundant naïve B cells, resting mast cells, resting CD4+ memory T cells, M2 macrophages, and monocytes in high-risk subgroups. The TIMER database showed strong positive correlations between PAK3,
FGF1, PRKD1, and PDGFRA expression levels and the infiltration of CD4+ T cells and macrophages. The IOBR analysis revealed an immunosuppressive environment in the high-risk subgroup. Low-risk patients show a higher response rate to anti-PD1 treatment. TMA showed that
FGF1 overexpression was associated with poor prognosis and CD4+ T cells and macrophage infiltration. In vivo study based on the 615 mice indicated that inhibiting
FGF1 function could suppress tumor growth and enhance anti-PD1 therapeutic efficacy. In summary, we established a five-angiogenesis-related gene model to predict survival outcomes and immunotherapy responses in patients with gastric cancer and identified
FGF1 as a prognostic gene and potential target for improving immune treatment.