Expression profiles of Annexin A1, formylated peptide receptors and cyclooxigenase-2 in gastroesophageal inflammations and neoplasias

Abstract

The anti-inflammatory protein Annexin-A1 (ANXA1) is associated to tumor invasion process and its actions can be mediated by formylated peptides receptors (FPRs). Therefore, we evaluated the expression and correlation of ANXA1, FPR and cyclooxygenase-2 (COX-2) enzyme in esophageal and stomach inflammations and neoplasias. The study of proteins was performed by immunohistochemistry in biopsies of esophagitis, Barrett's esophagus, squamous cell carcinoma and adenocarcinoma of the esophagus, as well as gastritis, stomach polypus and gastric adenocarcinoma. The intensity of the expressions was evaluated by densitometry. The immunohistochemical and densitometric analyzes showed specificity for the FPR1 receptor and modulation of the ANXA1, COX-2 and FPR1 expressions in the epithelial cells in the different studied conditions. Increased immunoreactivity of these proteins was observed in cases of inflammation and stomach polypus. Interestingly, moderate immunoreactivity for ANXA1 and FPR1 but increased immunolabeling for COX-2 were observed in Barrett́s esophagus and esophageal adenocarcinomas. Also, there was reduced expression of ANXA1 and FPR1 in esophageal carcinoma but COX-2 overexpression in this tumor. There was no expression of FPR2 but ANXA1 and FPR1 expressions were positively correlated in all clinical conditions studied. Positive correlation between ANXA1 and COX-2 were also observed in inflammation conditions while negative correlation between ANXA1 and COX-2 was observed in esophageal carcinoma. Our results demonstrate the unregulated expression of ANXA1 and COX-2 in precursor lesions of esophageal and stomach cancers, reinforcing their involvement in gastroesophageal carcinogenesis. In addition, the data show that the actions of ANXA1 in the inflammatory and neoplastic processes of the esophagus and stomach are specifically mediated by the FPR1 receptor.

Distinct Microbiota Dysbiosis in Patients with Non-Erosive Reflux Disease and Esophageal Adenocarcinoma

“…Proteins associated with stress response annexin-A1 and GSTP1 were also elevated. Annexin-A1 is considered a putative mediator of glucocorticoid immunosuppressive activity [ 31 ] and is associated with chronic inflammation in the esophagus [ 32 ], while the GSTP1 enzyme belongs to a supergene family of enzymes involved in protection of cells from oxidative stress. The GSTP1 enzyme is the most important form in the esophagus, with increased expression during acid reflux [ 33 ].…”

Low Annexin A1 Level in HTLV-1 Infected Patients is a Potential Biomarker for the Clinical Progression and Diagnosis of HAM/TSP

“…In addition to the association between ANXA1 mRNA transcription and HTLV-1 infection, a relationship was observed between infection and FPR mRNA levels. The interactions of these receptors with other ligands (both anti-and proin ammatory) enable the regulation of several pathological conditions, including tumorigenesis [35,36], in ammation [37] and some infectious processes [38].…”

Construction and Validation of a Prognostic Model of Gastric Cancer with 10RBPs Based on 6 Microarrays

“…Five RBPs with HR greater than 1 are considered dangerous genes (ANXA1, CDC20, EEF1A2, ITGB1, MYH11), and the other 5 RBPs with HR < 1 are considered protective genes (ACO1, AUH, CPEB3, DAZAP1, KIAA0101).According to reports, these hub RBPs play an important role in solid tumors. The compulsive ANXA1 expression in GC cells leads to cell growth inhibition, and at the same time acts on the development of GC by regulating the expression of COX-2 21,22 . CDC20 plays a key role in the occurrence and development of tumors, and high expression of CDC20 is often accompanied by a later stage and a worse prognosis and EEF1A2 is rarely found in normal gastric tissues, but is highly expressed in GC tissues 23,24 .…”