The prostaglandin receptor EP2 determines prognosis in EP3-negative and galectin-3-high cervical cancer cases

Sci Rep. 2020 Jan 24;10(1):1154. doi: 10.1038/s41598-020-58095-3.

Abstract

Recently our study identified EP3 receptor and galectin-3 as prognosticators of cervical cancer. The aim of the present study was the analysis of EP2 as a novel marker and its association to EP3, galectin-3, clinical pathological parameters and the overall survival rate of cervical cancer patients. Cervical cancer tissues (n = 250), as also used in our previous study, were stained with anti-EP2 antibodies employing a standardized immunohistochemistry protocol. Staining results were analyzed by the IRS scores and evaluated for its association with clinical-pathological parameters. H-test of EP2 percent-score showed significantly different expression in FIGO I-IV stages and tumor stages. Kaplan-Meier survival analyses indicated that EP3-negative/EP2-high staining patients (EP2 IRS score ≥2) had a significantly higher survival rate than the EP3-negative/EP2-low staining cases (p = 0.049). In the subgroup of high galectin-3 expressing patients, the group with high EP2 levels (IRS ≥2) had significantly better survival rates compared to EP2-low expressing group (IRS <2, p = 0.044). We demonstrated that the EP2 receptor is a prognostic factor for the overall survival in the subgroup of negative EP3 and high galectin-3 expressed cervical cancer patients. EP2 in combination with EP3 or galectin-3 might act as prognostic indicators of cervical cancer. EP2, EP3, and galectin-3 could be targeted for clinical diagnosis or endocrine treatment in cervical cancer patients, which demands future investigations.

MeSH terms

  • Adenocarcinoma / genetics
  • Adenocarcinoma / metabolism*
  • Adenocarcinoma / mortality
  • Adenocarcinoma / pathology
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / metabolism*
  • Carcinoma, Squamous Cell / mortality
  • Carcinoma, Squamous Cell / pathology
  • Female
  • Galectin 3 / analysis
  • Humans
  • Kaplan-Meier Estimate
  • Middle Aged
  • Neoplasm Proteins / analysis
  • Neoplasm Proteins / physiology*
  • Neoplasm Staging
  • Prognosis
  • Protein Isoforms / analysis
  • Receptors, Prostaglandin E, EP2 Subtype / physiology*
  • Receptors, Prostaglandin E, EP3 Subtype / deficiency
  • Receptors, Prostaglandin E, EP3 Subtype / genetics
  • Single-Blind Method
  • Survival Rate
  • Uterine Cervical Neoplasms / genetics
  • Uterine Cervical Neoplasms / metabolism*
  • Uterine Cervical Neoplasms / mortality
  • Uterine Cervical Neoplasms / pathology
  • Young Adult

Substances

  • Biomarkers, Tumor
  • Galectin 3
  • Neoplasm Proteins
  • PTGER2 protein, human
  • PTGER3 protein, human
  • Protein Isoforms
  • Receptors, Prostaglandin E, EP2 Subtype
  • Receptors, Prostaglandin E, EP3 Subtype