Revista de Investigación Clínica (Jan 2023)

Low expression of E-Cadherin and Cdh1 variants associated with diffuse gastric cancer

  • Azaria García-Ruvalcaba,
  • Katia C. Vázquez-Ibarra,
  • María T. Magaña-Torres,
  • Lourdes del C. Rizo de la Torre,
  • Lennon Meléndez-Aranda,
  • Gabriela López-Armas,
  • José A. Cruz-Ramos,
  • Jorge Peregrina-Sandoval,
  • Esther Espinoza-Jiménez,
  • María E. Rosales-Gradilla,
  • Josefina Y. Sánchez-López

DOI
https://doi.org/10.24875/RIC.22000257
Journal volume & issue
Vol. 75, no. 1

Abstract

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Background: Reduced or null expression of E-cadherin protein is a frequent cause of diffuse gastric cancer (DGC). More than 50% of patients with DGC present somatic variants in CDH1 gene. Objectives: The objectives of this study were to study E-cadherin expression and identify variants in the CDH1 gene in gastric tumors of patients with DGC. Methods: We studied 18 Mexican DGC patients who attended a hospital of the Mexican Social Security Institute; E-cadherin expression was determined by immunohistochemistry, and variants were identified by Sanger sequencing in promoter and coding regions. Predictive analysis was performed using PolyPhen-2 and HOPE software. Results: We found that 56% of DGC patients showed reduced expression of E-cadherin. All patients carried CDH1 variants; overall, 12 different CDH1 variants were identified. Predictive analysis revealed that the rs114265540 variant was probably damaging, with a value of 0.985, indicating a functional impact on the E-cadherin protein. Variants rs34939176 and rs33964119 were identified as risk factors for DGC (odds’ ratios [OR] = 31.3, 95% CI 6.3-154.0, p < 0.001; OR = 6.1, 95% CI 2.0-19.0, p < 0.001, respectively) given their elevated frequency and by comparing it with those reported for MXL population in the 1000 Genomes Project database. Conclusions: In this Mexican population, the percentage of diffuse gastric tumors with reduced expression of E-cadherin was similar to that reported in other populations. All gastric tumors of DGC patients studied had somatic CDH1 gene variants; however, the rs114265540, rs34939176, and rs33964119 variants were importantly related to DGC.

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