Low angiomotin-p130 with concomitant high Yes-associated protein 1 expression is associated with adverse prognosis of advanced gastric cancer

APMIS. 2017 Nov;125(11):996-1006. doi: 10.1111/apm.12750. Epub 2017 Sep 8.

Abstract

Angiomotin (AMOT) promotes angiogenesis and plays a role in neovascularization during tumorigenesis. Recently, the AMOT isoform, AMOT-p130, was shown to exert a regulatory effect on Yes-associated protein 1 (YAP1), a major downstream effector of the Hippo pathway. The specific roles of AMOT-p130 and YAP1 in advanced gastric cancer (AGC) are yet to be established. In this study, a total of 166 patients with AGC were enrolled, and AMOT-p130 and YAP1 levels were analyzed by immunohistochemistry using tissue microarrays. Low AMOT-p130 together with high YAP1 expression (n = 30, 18.1%) was associated with high T stage (p = 0.042), high TNM stage (p = 0.025), and venous invasion (p = 0.048). A Kaplan-Meier survival analysis with log-rank test revealed a significant correlation with decreased AMOT-p130 coupled with high nuclear YAP1 expression with shorter overall survival (p = 0.0045) and disease-free survival (p = 0.0028). Furthermore, multivariate analyses showed that the low AMOT-p130/high YAP1 expression profile was an independent prognostic factor for disease-free survival (p = 0.008, HR = 1.874, CI, 1.177-2.986) and overall survival (p = 0.012, HR = 1.903, CI, 1.152-3.143). Our findings collectively demonstrate that low AMOT-p130 combined with high YAP1 expression is correlated with an unfavorable AGC prognosis.

Keywords: Advanced gastric cancer; Yes-associated protein 1; angiomotin; immunohistochemistry.

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics*
  • Adenocarcinoma / diagnosis*
  • Adenocarcinoma / genetics
  • Adenocarcinoma / mortality
  • Adenocarcinoma / pathology
  • Aged
  • Angiomotins
  • Biomarkers, Tumor / genetics*
  • Female
  • Gene Expression
  • Humans
  • Intercellular Signaling Peptides and Proteins / genetics*
  • Kaplan-Meier Estimate
  • Male
  • Membrane Proteins / genetics*
  • Microfilament Proteins
  • Middle Aged
  • Multivariate Analysis
  • Neoplasm Staging
  • Neovascularization, Pathologic / diagnosis*
  • Neovascularization, Pathologic / genetics
  • Neovascularization, Pathologic / mortality
  • Neovascularization, Pathologic / pathology
  • Phosphoproteins / genetics*
  • Prognosis
  • Stomach Neoplasms / diagnosis*
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / mortality
  • Stomach Neoplasms / pathology
  • Transcription Factors
  • YAP-Signaling Proteins

Substances

  • AMOT protein, human
  • Adaptor Proteins, Signal Transducing
  • Angiomotins
  • Biomarkers, Tumor
  • Intercellular Signaling Peptides and Proteins
  • Membrane Proteins
  • Microfilament Proteins
  • Phosphoproteins
  • Transcription Factors
  • YAP-Signaling Proteins
  • YAP1 protein, human