Orexin A associates with inflammation by interacting with OX1R/OX2R receptor and activating prepro-Orexin in cancer tissues of gastric cancer patients

Gastroenterol Hepatol. 2020 May;43(5):240-247. doi: 10.1016/j.gastrohep.2019.10.006. Epub 2020 Jan 23.
[Article in English, Spanish]

Abstract

Objective: Gastric cancer (GC) has been become the second leading cause for cancer-associated death. This study aimed to investigate Orexin A levels and associated receptors in tumor tissues of GC patients.

Patients and methods: Forty-six consecutive gastric cancer patients (GC, n=46) and 13 chronic atrophic gastritis patients (CAG, n=13) were recruited. Meanwhile, 18 health individuals visiting Medical Examination Department were involved as control (N group, n=18). ELISA was used to examine Orexin A concentration. Immunohistochemistry assay was used to examine OX1R and OX2R. HE staining was applied to evaluate inflammation. qRT-PCR was employed to detect OX1R, OX2R, prepro-Orexin mRNAs. Serum Helicobacter pylori (H. pylori) infection was measured.

Results: Orexin A expression in GC patients was significantly up-regulated compared to N group and CAG group (p<0.05). Orexin A expression was increased in CAG group compared to N group (p<0.05). Gastric cancer tissues exhibited significantly obvious inflammation compared to N group and CAG group (p<0.05). OX1R and OX2R expressions were significantly down-regulated in GC group compared to N group and CAG group (p<0.05). OX1R and OX2R were lower significantly in GC group compared to CAG group (p<0.05). Prepro-Orexin was significantly depleted in tumor tissues of GC group compared to N group and CAG group (p<0.05). Orexin A expression was un-associated with gender, age and differential grades (p>0.05). CAG and GC patients demonstrated higher H. pylori infection rates.

Conclusion: Orexin A was associated with inflammation by interacting with OX1R/OX2R receptor and activating prepro-Orexin in tumor tissues of gastric cancer patients.

Keywords: Cáncer gástrico; Gastric cancer; OX1R; Orexin A; Orexina-A; Prepo-orexina; Prepro-Orexin.

MeSH terms

  • Female
  • Gastritis / complications
  • Gastritis / metabolism*
  • Gastritis, Atrophic / metabolism
  • Gene Expression Regulation, Neoplastic
  • Helicobacter Infections / complications
  • Helicobacter Infections / metabolism*
  • Helicobacter pylori*
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Proteins / biosynthesis
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / physiology*
  • Orexin Receptors / biosynthesis
  • Orexin Receptors / genetics
  • Orexin Receptors / physiology*
  • Orexins / biosynthesis
  • Orexins / genetics
  • Orexins / physiology*
  • Protein Precursors / metabolism*
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • Stomach Neoplasms / metabolism*
  • Stomach Neoplasms / microbiology
  • Stomach Neoplasms / pathology

Substances

  • HCRT protein, human
  • HCRTR1 protein, human
  • HCRTR2 protein, human
  • Neoplasm Proteins
  • Orexin Receptors
  • Orexins
  • Protein Precursors
  • RNA, Messenger