Identifying the signature of NAD+ metabolism-related genes for immunotherapy of gastric cancer

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-re...

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Main Authors: Huijuan Wen, Yang Mi, Fazhan Li, Xia Xue, Xiangdong Sun, Pengyuan Zheng, Simeng Liu
Format: Article
Language:English
Published: Elsevier 2024-10-01
Series:Heliyon
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Online Access:http://www.sciencedirect.com/science/article/pii/S2405844024148542
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author Huijuan Wen
Yang Mi
Fazhan Li
Xia Xue
Xiangdong Sun
Pengyuan Zheng
Simeng Liu
author_facet Huijuan Wen
Yang Mi
Fazhan Li
Xia Xue
Xiangdong Sun
Pengyuan Zheng
Simeng Liu
author_sort Huijuan Wen
collection DOAJ
description 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.
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spelling doaj-art-4ed9ff7f208a47fa82e95b5df380c91c2024-11-12T05:19:19ZengElsevierHeliyon2405-84402024-10-011020e38823Identifying the signature of NAD+ metabolism-related genes for immunotherapy of gastric cancerHuijuan Wen0Yang Mi1Fazhan Li2Xia Xue3Xiangdong Sun4Pengyuan Zheng5Simeng Liu6Henan 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, ChinaHenan 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, ChinaHenan 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, ChinaHenan 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, ChinaHenan 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, ChinaHenan 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.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.http://www.sciencedirect.com/science/article/pii/S2405844024148542APODGC prognosisImmunological biomarkersProliferationWnt/β-catenin/EMT signaling pathway
spellingShingle Huijuan Wen
Yang Mi
Fazhan Li
Xia Xue
Xiangdong Sun
Pengyuan Zheng
Simeng Liu
Identifying the signature of NAD+ metabolism-related genes for immunotherapy of gastric cancer
Heliyon
APOD
GC prognosis
Immunological biomarkers
Proliferation
Wnt/β-catenin/EMT signaling pathway
title Identifying the signature of NAD+ metabolism-related genes for immunotherapy of gastric cancer
title_full Identifying the signature of NAD+ metabolism-related genes for immunotherapy of gastric cancer
title_fullStr Identifying the signature of NAD+ metabolism-related genes for immunotherapy of gastric cancer
title_full_unstemmed Identifying the signature of NAD+ metabolism-related genes for immunotherapy of gastric cancer
title_short Identifying the signature of NAD+ metabolism-related genes for immunotherapy of gastric cancer
title_sort identifying the signature of nad metabolism related genes for immunotherapy of gastric cancer
topic APOD
GC prognosis
Immunological biomarkers
Proliferation
Wnt/β-catenin/EMT signaling pathway
url http://www.sciencedirect.com/science/article/pii/S2405844024148542
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