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

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 g...

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Main Authors: Azaria García-Ruvalcaba (Author), Katia C. Vázquez-Ibarra (Author), María T. Magaña-Torres (Author), Lourdes del C. Rizo de la Torre (Author), Lennon Meléndez-Aranda (Author), Gabriela López-Armas (Author), José A. Cruz-Ramos (Author), Jorge Peregrina-Sandoval (Author), Esther Espinoza-Jiménez (Author), María E. Rosales-Gradilla (Author), Josefina Y. Sánchez-López (Author)
Format: Book
Published: Permanyer, 2023-01-01T00:00:00Z.
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Summary: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.
Item Description:10.24875/RIC.22000257
0034-8376
2564-8896

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