Low expression of e-cadherin and cdh1 variants associated with diffuse gastric cancer

• Azaria García Ruvalcaba ^[1] ; Katia C. Vázquez-Ibarra ^[1] ; María T. Magaña-Torres ^[2] ; Lourdes del C. Rizo de la Torre ^[2] ; Lennon Meléndez-Aranda ^[2] ; Gabriela López-Armas ^[3] ; José A. Cruz-Ramos ^[4] ; Jorge Peregrina-Sandoval ^[1] ; Esther Espinoza-Jiménez ^[5] ; María E. Rosales-Gradilla ^[6] ; Josefina Y. Sánchez-López ^[2]
  1. [1] Universidad de Guadalajara

     Universidad de Guadalajara

     México

     
  2. [2] Instituto Mexicano del Seguro Social

     Instituto Mexicano del Seguro Social

     México

     
  3. [3] Industrial Technical Education Center, Guadalajara
  4. [4] Immunobiology Laboratory, Department of Cellular and Molecular Biology, Jalisco Institute of Cancerology, Guadalajara
  5. [5] Department of Pathology, General Regional Hospital 110, IMSS, Guadalajara
  6. [6] Department of Pathology, National Western Medical Center, IMSS, Guadalajara, Jal., Mexico

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• Localización: Revista de investigación clínica, ISSN 0034-8376, ISSN-e 2564-8896, Vol. 75, Nº. 1, 2023, págs. 37-44
• Idioma: inglés
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• Resumen

  • 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.