The Third Central Clinical College of Tianjin Medical University, Tianjin, China.
The Third Central Hospital of Tianjin, Tianjin, China.
PeerJ. 2024 Jul 31;12:e17833. doi: 10.7717/peerj.17833. eCollection 2024.
This study endeavored to develop a nicotinamide adenine dinucleotide (NAD+) metabolism-related biomarkers in gastric cancer (GC), which could provide a theoretical foundation for prognosis and therapy of GC patients.
In this study, differentially expressed genes (DEGs1) between GC and paraneoplastic tissues were overlapped with NAD+ metabolism-related genes (NMRGs) to identify differentially expressed NMRGs (DE-NMRGs). Then, GC patients were divided into high and low score groups by gene set variation analysis (GSVA) algorithm for differential expression analysis to obtain DEGs2, which was overlapped with DEGs1 for identification of intersection genes. These genes were further analyzed using univariate Cox and least absolute shrinkage and selection operator (LASSO) regression analyses to obtain prognostic genes for constructing a risk model. Enrichment and immune infiltration analyses further investigated investigate the different risk groups, and qRT-PCR validated the prognostic genes.
Initially, we identified DE-NMRGs involved in NAD biosynthesis, with seven ( and ) showing prognostic significance in GC. Subsequent, a prognostic model was constructed in which the risk score, derived from the expression profiles of these genes, along with gender, emerged as robust independent predictors of patient outcomes in GC. Enrichment analysis linked high-risk patients to synaptic membrane pathways and low-risk to the CMG complex pathway. Tumor immune infiltration analysis revealed correlations between risk scores and immune cell abundance, suggesting a relationship between NAD+ metabolism and immune response in GC. The prognostic significance of our identified genes was validated by qRT-PCR, which confirmed their upregulated expression in GC tissue samples.
In this study, seven NAD+ metabolism-related markers were established, which is of great significance for the development of prognostic molecular biomarkers and clinical prognosis prediction for gastric cancer patients.
本研究旨在构建胃癌（GC）中烟酰胺腺嘌呤二核苷酸（NAD+）代谢相关生物标志物，为 GC 患者的预后和治疗提供理论基础。
本研究首先将 GC 与癌旁组织的差异表达基因（DEGs1）与 NAD+代谢相关基因（NMRGs）重叠，以识别差异表达的 NMRGs（DE-NMRGs）。然后，通过基因集变异分析（GSVA）算法对 GC 患者进行分组，对差异表达分析获得 DEGs2，并与 DEGs1 进行重叠以识别交集基因。进一步对这些基因进行单变量 Cox 和最小绝对值收缩和选择算子（LASSO）回归分析，以获得构建风险模型的预后基因。富集和免疫浸润分析进一步探讨不同风险组，并通过 qRT-PCR 验证预后基因。
首先，我们鉴定了参与 NAD 生物合成的 DE-NMRGs，其中 7 个（和）在 GC 中具有预后意义。随后，构建了一个预后模型，其中风险评分由这些基因的表达谱以及性别组成，是 GC 患者预后的稳健独立预测因子。富集分析将高风险患者与突触膜途径相关联，而低风险患者与 CMG 复合物途径相关联。肿瘤免疫浸润分析显示风险评分与免疫细胞丰度之间存在相关性，提示 GC 中 NAD+代谢与免疫反应之间存在关联。qRT-PCR 验证了我们鉴定的基因的预后意义，证实了它们在 GC 组织样本中的上调表达。
本研究建立了 7 个 NAD+代谢相关标志物，对 GC 患者预后分子标志物的开发和临床预后预测具有重要意义。
