Wen Huijuan, Mi Yang, Li Fazhan, Xue Xia, Sun Xiangdong, Zheng Pengyuan, Liu Simeng
Henan Key Laboratory of Helicobacter pylori & Microbiota and Gastrointestinal Cancer, Marshall Medical Research Center, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.
Academy of medical science, Zhengzhou University, Zhengzhou, 450052, China.
Heliyon. 2024 Oct 2;10(20):e38823. doi: 10.1016/j.heliyon.2024.e38823. eCollection 2024 Oct 30.
NAD (Nicotinamide Adenine Dinucleotide) -related metabolic reprogramming in tumor cells involves multiple vital cellular processes. However, the role of NAD metabolism in immunity and the prognosis of gastric cancer (GC) remains not elucidated. Here we identified and clustered 33 NAD + metabolism-related genes (NMRGs) based on 808 GC samples from the Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases. Survival analysis between different groups found a poor prognosis in the GC patients with high NMRGs expression. Gene , , and were identified and performed high expression in GC samples, while the qRT-PCR results further confirmed that their expression levels in GC cell lines were significantly higher than those from normal human gastric mucosa epithelial cells. Based on the single-cell analysis, Gene , , and can potentially be novel biomarkers of tumor-associated fibroblasts (CAFs). In parallel, the proliferation and migration of GC cells were significantly hampered following the knockdown of , , and , particularly , we confirmed that knockdown can inhibit β-catenin and N-cadherin expression, while promote E-cadherin expression. This study unveils a novel NMRGs-related gene signature, highlighting as a prognostic biomarker linked to the tumor microenvironment. drives GC cell proliferation and metastasis through the Wnt/β-catenin/EMT signaling pathway, establishing it as a promising therapeutic target for GC patients.
肿瘤细胞中与烟酰胺腺嘌呤二核苷酸（NAD）相关的代谢重编程涉及多个重要的细胞过程。然而，NAD代谢在免疫及胃癌（GC）预后中的作用仍未阐明。在此，我们基于来自癌症基因组图谱（TCGA）和基因表达综合数据库（GEO）的808份GC样本，鉴定并聚类了33个与NAD+代谢相关的基因（NMRGs）。不同组间的生存分析发现，NMRGs高表达的GC患者预后较差。鉴定出基因、和在GC样本中高表达，qRT-PCR结果进一步证实它们在GC细胞系中的表达水平显著高于正常人胃黏膜上皮细胞。基于单细胞分析，基因、和可能是肿瘤相关成纤维细胞（CAFs）的新型生物标志物。同时，敲低、和后，尤其是，GC细胞的增殖和迁移受到显著抑制，我们证实敲低可抑制β-连环蛋白和N-钙黏蛋白表达，同时促进E-钙黏蛋白表达。本研究揭示了一种新型的与NMRGs相关的基因特征，突出了作为与肿瘤微环境相关的预后生物标志物的作用。通过Wnt/β-连环蛋白/上皮-间质转化（EMT）信号通路驱动GC细胞增殖和转移，使其成为GC患者有前景的治疗靶点。
