Neural precursor cell-expressed developmentally down-regulated 4-like: a new biomarker in the pathophysiology of endometrial cancer

J Int Med Res. 2018 Sep;46(9):3709-3716. doi: 10.1177/0300060518777944. Epub 2018 Jul 12.

Abstract

Objectives Endometrial cancer is the most frequent tumor of the female genital tract. Ubiquitin is a small protein (8.5 kDa) found in all eukaryotic cells, binds to substrate proteins via a three-phase enzymatic pathway referred to as ubiquitination and plays an important role in cellular stability. Neural precursor cell-expressed developmentally down-regulated 4-like (NEDD4L) functions in the last phase of this enzymatic process. In this study, we investigated NEDD4L protein expression in endometrial cancer. Methods The study participants were divided into patients with benign endometrial pathologies (Group 1, n = 23), patients with endometrial hyperplasia (Group 2, n = 21) and patients with endometrial cancer (Group 3, n = 20). NEDD4L expression was detected by immunohistochemical staining and H scores were calculated to standardize staining intensity. Statistical analysis was performed using SPSS 16.0. Results NEDD4L expression levels according to H scores were significantly lower in patients diagnosed with endometrial cancer compared with those with benign endometrial pathologies. Conclusion NEDD4L is involved in maintaining cell stability, and reduced NEDD4L expression as a result of gene mutation may disrupt this balance in favor of tumorigenesis.

Keywords: NEDD4L; endometrial cancer; endometrial hyperplasia; immunohistochemistry; tumorigenesis; ubiquitin.

MeSH terms

  • Adenocarcinoma / genetics
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology
  • Adenocarcinoma / physiopathology*
  • Adult
  • Aged
  • Endometrial Hyperplasia / genetics
  • Endometrial Hyperplasia / pathology
  • Endometrial Hyperplasia / physiopathology
  • Endometrial Neoplasms / genetics
  • Endometrial Neoplasms / metabolism
  • Endometrial Neoplasms / pathology
  • Endometrial Neoplasms / physiopathology*
  • Female
  • Gene Expression
  • Humans
  • Immunohistochemistry
  • Middle Aged
  • Nedd4 Ubiquitin Protein Ligases / biosynthesis
  • Nedd4 Ubiquitin Protein Ligases / genetics*
  • Polyps / genetics
  • Polyps / metabolism
  • Polyps / pathology
  • Polyps / physiopathology
  • Retrospective Studies
  • Uterine Diseases / genetics
  • Uterine Diseases / metabolism
  • Uterine Diseases / pathology
  • Uterine Diseases / physiopathology

Substances

  • Nedd4 Ubiquitin Protein Ligases
  • Nedd4 protein, human