Alterations in vitamin D signaling pathway in gastric cancer progression: a study of vitamin D receptor expression in human normal, premalignant, and malignant gastric tissue

Int J Clin Exp Pathol. 2015 Oct 1;8(10):13176-84. eCollection 2015.

Abstract

Amount of studies in cells and animal models have proved vitamin D has multifarious antitumor effects. However, epidemiological studies showed inconsistent result on gastric cancer. The antitumor role is mainly mediated by the vitamin D receptor (VDR). Our hypothesis is that VDR may be abnormally (poorly) expressed in gastric cancer tissue. Present study is aimed at discovering and analyzing VDR expression in a series of human gastric tissues, including normal, premalignant, and malignant gastric tissue, and correlated VDR to the clinicopathological parameters of gastric cancer patients. VDR expression was detected by immunohistochemistry. The χ(2) test was used to analyze the VDR expression as well as the relationship between VDR and the clinicopathological factors of gastric cancer patients. Compared with normal (82.61%) and premalignant tissues (73.64%), VDR was lower expressed in cancer tissues (57.61%), with a statistically significant difference (P = 0.001). Among cancer tissues, VDR was higher expressed in well and moderate differentiated tissues contrasted with tissues with poor differentiation, and higher expressed in small tumors (< 5 cm) compared with large tumors (≥ 5 cm), with a statistically significant difference respectively (P = 0.016, P = 0.009). A decline linear trend appeared when analyzing the statistical difference of VDR expression among normal, premalignant, and malignant gastric tissues. VDR expression has been on the decline from the premalignant stage, finally low expressed in gastric cancer tissues, especial in poorly differentiated tissues. VDR could be a potential prognostic factor for patients with gastric cancer.

Keywords: Vitamin D; antitumor; gastric cancer; immunohistochemistry; vitamin D receptor.

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / analysis*
  • Disease Progression
  • Female
  • Gastric Mucosa / metabolism
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Precancerous Conditions / metabolism
  • Precancerous Conditions / pathology*
  • Receptors, Calcitriol / analysis
  • Receptors, Calcitriol / biosynthesis*
  • Signal Transduction / physiology
  • Stomach Neoplasms / metabolism
  • Stomach Neoplasms / pathology*

Substances

  • Biomarkers, Tumor
  • Receptors, Calcitriol