胃癌（GC）因其广泛患病率和不良预后而构成全球健康挑战。尽管免疫疗法在临床环境中显示出希望，但其疗效仍然仅限于少数胃癌患者。锰因其在人体抗肿瘤免疫反应中的作用而被认可，当与免疫检查点抑制剂联合使用时，有可能增强肿瘤治疗的有效性。基因表达综合（GEO）和癌症基因组图谱（TCGA）数据库被用来获取 GC 的转录组信息和临床数据。采用无监督聚类将样本分层为不同的亚型。通过单变量 Cox 回归和最小绝对收缩和选择算子 (LASSO) 回归分析，在 GC 中鉴定了锰代谢和免疫相关基因 (MIRG)。我们进行了基因组变异分析，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。通过单细胞RNA测序数据和细胞实验进一步分析了NPR3在GC中的潜在作用。GC患者被分为四种亚型，其特征是预后和肿瘤微环境显着不同。 13 个基因被鉴定并建立为 MIRG，在 GC 患者中表现出卓越的预测效果。在不同的风险亚组中观察到分子功能和途径的独特富集模式。免疫浸润分析显示高危组中巨噬细胞和单核细胞的丰度显着增加。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会从免疫治疗中受益。 NPR3的表达在GC组织中显着下调。单细胞RNA测序分析表明NPR3的表达分布在内皮细胞中。细胞实验表明，NPR3 促进 GC 细胞增殖。这是第一项利用锰代谢和免疫相关基因来鉴定 GC 预后 MIRG 的研究。 MIRG 不仅可靠地预测了 GC 患者的临床结果，而且有可能指导这些患者未来的免疫治疗干预。版权所有 © 2024 Han、Leng、Zhao、Wang、Chen、Wang、Zhang、Li、Lu、Wang 和 Qi 。

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.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 NPR3 in GC was further analyzed in the single-cell RNA sequencing data and cellular experiments.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. NPR3 expression was significantly downregulated in GC tissues. Single-cell RNA sequencing analysis indicated that the expression of NPR3 was distributed in endothelial cells. Cellular experiments demonstrated that NPR3 facilitated the proliferation of GC cells.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.Copyright © 2024 Han, Leng, Zhao, Wang, Chen, Wang, Zhang, Li, Lu, Wang and Qi.