Norepinephrine Enhances Aerobic Glycolysis and May Act as a Predictive Factor for Immunotherapy in Gastric Cancer
Objective/Background and Aims. The gastrointestinal tract is rich in neurotransmitters, which play an essential role in the occurrence and development of gastrointestinal tumors. We aimed to explore the function of neurotransmitters in gastric cancer and identify a suitable target to treat gastric c...
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| Format: | Article |
| Language: | English |
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Wiley
2021-01-01
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| Series: | Journal of Immunology Research |
| Online Access: | http://dx.doi.org/10.1155/2021/5580672 |
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| author | Yangyang Wang Shuchang Wang Qin Yang Jun Li Fengrong Yu Enhao Zhao |
| author_facet | Yangyang Wang Shuchang Wang Qin Yang Jun Li Fengrong Yu Enhao Zhao |
| author_sort | Yangyang Wang |
| collection | DOAJ |
| description | Objective/Background and Aims. The gastrointestinal tract is rich in neurotransmitters, which play an essential role in the occurrence and development of gastrointestinal tumors. We aimed to explore the function of neurotransmitters in gastric cancer and identify a suitable target to treat gastric cancer patients in the future. Methods. Monoamine neurotransmitters were detected in gastric cancer tissue and paired normal tissue, and The Cancer Genome Atlas was used to identify differentially expressed norepinephrine-degrading and synthetic enzymes. Quantitative real-time PCR and the Seahorse assay were used to determine the effect of norepinephrine on gastric cancer cell glycolysis. MAOA expression in cancer tissues was analyzed by immunohistochemistry and was compared with the patient SUVmax value of PET-CT and other clinicopathological characteristics. Results. The norepinephrine levels were markedly high in gastric cancer tissue, while the norepinephrine-degrading enzymes MAOA and MAOB showed low expression. High norepinephrine levels were associated with activated glycolysis. The MAOA or MAOB expression levels in tumor tissue were closely correlated with the patient SUV max values of PET-CT and immunotherapy evaluation indices, such as PD-L1 and the microsatellite status. Conclusions. Norepinephrine shows relatively higher expression in gastric cancer tissue than in normal tissue, and its expression level is associated with the glycolysis levels in patients. The norepinephrine-degrading enzymes MAOA and MAOB have significant expression differences in cancer and normal tissue, and their missing or low expression may predict immune therapy outcomes for gastric cancer patients. High norepinephrine levels with metabolic abnormalities may be more suitable for metabolic targeted therapy or immunotherapy. |
| format | Article |
| id | doaj-art-df0786b254e84b3a900225ceed0dd164 |
| institution | OA Journals |
| issn | 2314-8861 2314-7156 |
| language | English |
| publishDate | 2021-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Immunology Research |
| spelling | doaj-art-df0786b254e84b3a900225ceed0dd1642025-08-20T02:21:06ZengWileyJournal of Immunology Research2314-88612314-71562021-01-01202110.1155/2021/55806725580672Norepinephrine Enhances Aerobic Glycolysis and May Act as a Predictive Factor for Immunotherapy in Gastric CancerYangyang Wang0Shuchang Wang1Qin Yang2Jun Li3Fengrong Yu4Enhao Zhao5Department of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, ChinaDepartment of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, ChinaState Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200240, ChinaState Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200240, ChinaDepartment of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, ChinaDepartment of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, ChinaObjective/Background and Aims. The gastrointestinal tract is rich in neurotransmitters, which play an essential role in the occurrence and development of gastrointestinal tumors. We aimed to explore the function of neurotransmitters in gastric cancer and identify a suitable target to treat gastric cancer patients in the future. Methods. Monoamine neurotransmitters were detected in gastric cancer tissue and paired normal tissue, and The Cancer Genome Atlas was used to identify differentially expressed norepinephrine-degrading and synthetic enzymes. Quantitative real-time PCR and the Seahorse assay were used to determine the effect of norepinephrine on gastric cancer cell glycolysis. MAOA expression in cancer tissues was analyzed by immunohistochemistry and was compared with the patient SUVmax value of PET-CT and other clinicopathological characteristics. Results. The norepinephrine levels were markedly high in gastric cancer tissue, while the norepinephrine-degrading enzymes MAOA and MAOB showed low expression. High norepinephrine levels were associated with activated glycolysis. The MAOA or MAOB expression levels in tumor tissue were closely correlated with the patient SUV max values of PET-CT and immunotherapy evaluation indices, such as PD-L1 and the microsatellite status. Conclusions. Norepinephrine shows relatively higher expression in gastric cancer tissue than in normal tissue, and its expression level is associated with the glycolysis levels in patients. The norepinephrine-degrading enzymes MAOA and MAOB have significant expression differences in cancer and normal tissue, and their missing or low expression may predict immune therapy outcomes for gastric cancer patients. High norepinephrine levels with metabolic abnormalities may be more suitable for metabolic targeted therapy or immunotherapy.http://dx.doi.org/10.1155/2021/5580672 |
| spellingShingle | Yangyang Wang Shuchang Wang Qin Yang Jun Li Fengrong Yu Enhao Zhao Norepinephrine Enhances Aerobic Glycolysis and May Act as a Predictive Factor for Immunotherapy in Gastric Cancer Journal of Immunology Research |
| title | Norepinephrine Enhances Aerobic Glycolysis and May Act as a Predictive Factor for Immunotherapy in Gastric Cancer |
| title_full | Norepinephrine Enhances Aerobic Glycolysis and May Act as a Predictive Factor for Immunotherapy in Gastric Cancer |
| title_fullStr | Norepinephrine Enhances Aerobic Glycolysis and May Act as a Predictive Factor for Immunotherapy in Gastric Cancer |
| title_full_unstemmed | Norepinephrine Enhances Aerobic Glycolysis and May Act as a Predictive Factor for Immunotherapy in Gastric Cancer |
| title_short | Norepinephrine Enhances Aerobic Glycolysis and May Act as a Predictive Factor for Immunotherapy in Gastric Cancer |
| title_sort | norepinephrine enhances aerobic glycolysis and may act as a predictive factor for immunotherapy in gastric cancer |
| url | http://dx.doi.org/10.1155/2021/5580672 |
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