Identifying the signature of NAD+ metabolism-related genes for immunotherapy of gastric cancer
Huijuan Wen,
Yang Mi,
Fazhan Li,
Xia Xue,
Xiangdong Sun,
Pengyuan Zheng,
Simeng Liu
Affiliations
Huijuan Wen
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
Yang Mi
Henan Key Laboratory of Helicobacter pylori & Microbiota and Gastrointestinal Cancer, Marshall Medical Research Center, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China; Department of Gastroenterology, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China
Fazhan Li
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
Xia Xue
Henan Key Laboratory of Helicobacter pylori & Microbiota and Gastrointestinal Cancer, Marshall Medical Research Center, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China; Department of Gastroenterology, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China
Xiangdong Sun
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
Pengyuan Zheng
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; Department of Gastroenterology, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China; Corresponding author. Henan Key Laboratory of Helicobacter pylori & Microbiota and Gastrointestinal Cancer, Marshall Medical Research Center, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.
Simeng Liu
Henan Key Laboratory of Helicobacter pylori & Microbiota and Gastrointestinal Cancer, Marshall Medical Research Center, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China; Department of Gastroenterology, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China; Corresponding author. Henan Key Laboratory of Helicobacter pylori & Microbiota and Gastrointestinal Cancer, Marshall Medical Research Center, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.
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 SGCE, APOD, and PPP1R14A 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 SGCE, APOD, and PPP1R14A 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 SGCE, APOD, and PPP1R14A, particularly APOD, we confirmed that APOD knockdown can inhibit β-catenin and N-cadherin expression, while promote E-cadherin expression. This study unveils a novel NMRGs-related gene signature, highlighting APOD as a prognostic biomarker linked to the tumor microenvironment. APOD drives GC cell proliferation and metastasis through the Wnt/β-catenin/EMT signaling pathway, establishing it as a promising therapeutic target for GC patients.
