开发和验证与锰代谢和免疫相关的基因标志物，用于预测胃癌的预后和免疫图谱。

BACKGROUND: Gastric cancer (GC) poses a global health challenge due to its widespread prevalence and unfavorable prognosis. Although immunotherapy has shown promise in clinical settings, its efficacy remains limited to a minority of GC patients. Manganese, recognized for its role in the body's anti-tumor immune response, has the potential to enhance the effectiveness of tumor treatment when combined with immune checkpoint inhibitors. METHODS: Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases was utilized to obtain transcriptome information and clinical data for GC. Unsupervised clustering was employed to stratify samples into distinct subtypes. Manganese metabolism- and immune-related genes (MIRGs) were identified in GC by univariate Cox regression and least absolute shrinkage and selection operator (LASSO) regression analysis. We conducted gene set variation analysis, and assessed the immune landscape, drug sensitivity, immunotherapy efficacy, and somatic mutations. The underlying role of in GC was further analyzed in the single-cell RNA sequencing data and cellular experiments. RESULTS: GC patients were classified into four subtypes characterized by significantly different prognoses and tumor microenvironments. Thirteen genes were identified and established as MIRGs, demonstrating exceptional predictive effectiveness in GC patients. Distinct enrichment patterns of molecular functions and pathways were observed among various risk subgroups. Immune infiltration analysis revealed a significantly greater abundance of macrophages and monocytes in the high-risk group. Drug sensitivity analysis identified effective drugs for patients, while patients in the low-risk group could potentially benefit from immunotherapy. expression was significantly downregulated in GC tissues. Single-cell RNA sequencing analysis indicated that the expression of was distributed in endothelial cells. Cellular experiments demonstrated that facilitated the proliferation of GC cells. CONCLUSION: This is the first study to utilize manganese metabolism- and immune-related genes to identify the prognostic MIRGs for GC. The MIRGs not only reliably predicted the clinical outcome of GC patients but also hold the potential to guide future immunotherapy interventions for these patients.

背景：胃癌（GC）由于其广泛的流行和不良的预后，是一个全球性的健康挑战。尽管免疫疗法在临床环境中显示出了前景，但它的疗效仍然局限于少数 GC 患者。锰作为人体抗肿瘤免疫反应的一部分，当与免疫检查点抑制剂结合使用时，有可能增强肿瘤治疗的效果。

方法：使用基因表达综合（GEO）和癌症基因组图谱（TCGA）数据库获取 GC 的转录组信息和临床数据。使用无监督聚类将样本分为不同的亚型。通过单因素 Cox 回归和最小绝对值收缩和选择算子（LASSO）回归分析，在 GC 中鉴定锰代谢和免疫相关基因（MIRGs）。我们进行了基因集变异分析，并评估了免疫景观、药物敏感性、免疫治疗效果和体细胞突变。进一步在单细胞 RNA 测序数据和细胞实验中分析了在 GC 中的作用。

结果：GC 患者分为四个具有显著不同预后和肿瘤微环境的亚型。鉴定出 13 个基因，并将其建立为 MIRGs，在 GC 患者中表现出出色的预测效果。在不同风险亚组中观察到分子功能和途径的明显富集模式。免疫浸润分析显示高风险组中巨噬细胞和单核细胞的丰度显著增加。药物敏感性分析确定了对患者有效的药物，而低风险组的患者可能受益于免疫治疗。在 GC 组织中表达显著下调。单细胞 RNA 测序分析表明在 GC 组织中表达分布于内皮细胞。细胞实验表明促进了 GC 细胞的增殖。

结论：这是第一项利用锰代谢和免疫相关基因来鉴定 GC 预后 MIRGs 的研究。这些 MIRGs 不仅可靠地预测了 GC 患者的临床结局，而且有可能为这些患者的未来免疫治疗干预提供指导。