Norepinephrine Enhances Aerobic Glycolysis and May Act as a Predictive Factor for Immunotherapy in Gastric Cancer

J Immunol Res. 2021 Mar 27:2021:5580672. doi: 10.1155/2021/5580672. eCollection 2021.

Abstract

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.

Publication types

  • Observational Study

MeSH terms

  • Antimetabolites, Antineoplastic
  • Antineoplastic Agents, Immunological
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • B7-H1 Antigen / antagonists & inhibitors
  • B7-H1 Antigen / metabolism
  • Cell Line, Tumor
  • Gastric Mucosa / enzymology
  • Gastric Mucosa / immunology
  • Gastric Mucosa / pathology
  • Humans
  • Immunohistochemistry
  • Monoamine Oxidase / analysis
  • Monoamine Oxidase / metabolism
  • Norepinephrine / analysis
  • Norepinephrine / metabolism*
  • Positron Emission Tomography Computed Tomography
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors
  • Programmed Cell Death 1 Receptor / metabolism
  • Stomach Neoplasms / drug therapy
  • Stomach Neoplasms / immunology*
  • Stomach Neoplasms / pathology
  • Treatment Outcome
  • Tumor Microenvironment / drug effects
  • Tumor Microenvironment / immunology
  • Warburg Effect, Oncologic*

Substances

  • Antimetabolites, Antineoplastic
  • Antineoplastic Agents, Immunological
  • B7-H1 Antigen
  • CD274 protein, human
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor
  • Monoamine Oxidase
  • monoamine oxidase A, human
  • Norepinephrine