Clinicopathological significance of RCAN2 production in gastric carcinoma

Histopathology. 2019 Feb;74(3):430-442. doi: 10.1111/his.13764.

Abstract

Aims: Gastric cancer (GC) is one of the leading causes of cancer-related death worldwide. Genes expressed only in cancer tissue may be useful biomarkers for cancer diagnosis and therapeutics. The aims of the present study were to analyse regulator of calcineurin 2 (RCAN2) in a large number of GCs, and to investigate how these expression patterns correlate with clinicopathological parameters and various markers.

Methods and results: An immunohistochemical analysis of RCAN2 in 207 GC tissue samples showed that 110 (53%) GCs were positive for RCAN2. RCAN2-positive GCs were more advanced in terms of TNM classification and tumour stage than RCAN2-negative GCs. Furthermore, RCAN2 was an independent prognostic classifier for GC patients. The cell growth and invasiveness of RCAN2 small interfering RNA (siRNA)-transfected GC cell lines were less than those of the negative control siRNA-transfected cell lines, whereas those of RCAN2-transfected cells were significantly increased as compared with those of empty vector-transfected cells. RCAN2 siRNA inhibits the phosphorylation of AKT and p44/p42 (ERK1/2). RCAN2 was colocalised with EGFR, nuclear β-catenin, MMP7, laminin-γ2, VEGF-A, and VEGF-C.

Conclusion: These results suggest that RCAN2 is involved in tumour progression and is an independent prognostic classifier in patients with GC.

Keywords: Helicobacter pylori; RCAN2; calcineurin-NFATc signalling pathway; gastric cancer.

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / analysis
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Muscle Proteins / biosynthesis*
  • Prognosis
  • Proportional Hazards Models
  • Retrospective Studies
  • Stomach Neoplasms / pathology*

Substances

  • Biomarkers, Tumor
  • Muscle Proteins
  • RCAN2 protein, human