E-cadherin genetic variants predict survival outcome in breast cancer patients

Hager Memni, Yosra Macherki, Zahra Klayech, Ahlem Ben-Haj-Ayed, Karim Farhat, Yassmine Remadi, Sallouha Gabbouj, Wijden Mahfoudh, Nadia Bouzid, Noureddine Bouaouina, Lotfi Chouchane, Abdelfattah Zakhama, Elham Hassen

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Background: E-cadherin is a major component of adherens junctions that regulates cell shape and maintains tissue integrity. A complete loss or any decrease in cell surface expression of E-cadherin will interfere with the cell-to-cell junctions' strength and leads to cell detachment and escape from the primary tumor site. In this prospective study, three functional single nucleotide polymorphisms (-347G/GA, rs5030625; -160C/A, rs16260; +54C/T, rs1801026), were found to modulate E-cadherin expression. Methods: 577 DNA samples from breast cancer (BC) cases were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results: We detected no significant correlations between each polymorphism and the clinical parameters of the patients whereas the GACC haplotype was significantly associated with low SBR grading. Overall survival analysis showed that both -347G/G and +54C/C wild (wt) genotypes had a significantly worse effect compared to the other genotypes (non-wt). Moreover, carrying simultaneously both the -347 and +54 wt genotypes confers a significantly higher risk of death. However, with metastatic recurrence, the death-rate was null in patients carrying the non-wt genotypes, and attained 37% in those carrying the wt genotype. A multivariate analysis showed that these two polymorphisms are independent prognostic factors for overall survival in BC patients. Conclusions: Our results support the fact that E-cadherin genetic variants control disease severity and progression and could be a marker of disease outcome. These findings could be useful in selecting patients that should be monitored differently.

Original languageEnglish
Article number320
JournalJournal of Translational Medicine
Volume14
Issue number1
DOIs
Publication statusPublished - 16 Nov 2016

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Cadherins
Polymorphism
Genotype
Breast Neoplasms
Survival
Disease control
Polymerase chain reaction
Tumor Escape
Adherens Junctions
Intercellular Junctions
Cell Shape
Tumors
Survival Analysis
Nucleotides
Restriction Fragment Length Polymorphisms
Haplotypes
Single Nucleotide Polymorphism
Disease Progression
Tissue
Multivariate Analysis

Keywords

  • Breast cancer
  • E-cadherin
  • Prognosis
  • SNP

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Memni, H., Macherki, Y., Klayech, Z., Ben-Haj-Ayed, A., Farhat, K., Remadi, Y., ... Hassen, E. (2016). E-cadherin genetic variants predict survival outcome in breast cancer patients. Journal of Translational Medicine, 14(1), [320]. https://doi.org/10.1186/s12967-016-1077-4

E-cadherin genetic variants predict survival outcome in breast cancer patients. / Memni, Hager; Macherki, Yosra; Klayech, Zahra; Ben-Haj-Ayed, Ahlem; Farhat, Karim; Remadi, Yassmine; Gabbouj, Sallouha; Mahfoudh, Wijden; Bouzid, Nadia; Bouaouina, Noureddine; Chouchane, Lotfi; Zakhama, Abdelfattah; Hassen, Elham.

In: Journal of Translational Medicine, Vol. 14, No. 1, 320, 16.11.2016.

Research output: Contribution to journalArticle

Memni, H, Macherki, Y, Klayech, Z, Ben-Haj-Ayed, A, Farhat, K, Remadi, Y, Gabbouj, S, Mahfoudh, W, Bouzid, N, Bouaouina, N, Chouchane, L, Zakhama, A & Hassen, E 2016, 'E-cadherin genetic variants predict survival outcome in breast cancer patients', Journal of Translational Medicine, vol. 14, no. 1, 320. https://doi.org/10.1186/s12967-016-1077-4
Memni H, Macherki Y, Klayech Z, Ben-Haj-Ayed A, Farhat K, Remadi Y et al. E-cadherin genetic variants predict survival outcome in breast cancer patients. Journal of Translational Medicine. 2016 Nov 16;14(1). 320. https://doi.org/10.1186/s12967-016-1077-4
Memni, Hager ; Macherki, Yosra ; Klayech, Zahra ; Ben-Haj-Ayed, Ahlem ; Farhat, Karim ; Remadi, Yassmine ; Gabbouj, Sallouha ; Mahfoudh, Wijden ; Bouzid, Nadia ; Bouaouina, Noureddine ; Chouchane, Lotfi ; Zakhama, Abdelfattah ; Hassen, Elham. / E-cadherin genetic variants predict survival outcome in breast cancer patients. In: Journal of Translational Medicine. 2016 ; Vol. 14, No. 1.
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AU - Remadi, Yassmine

AU - Gabbouj, Sallouha

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AU - Bouzid, Nadia

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AB - Background: E-cadherin is a major component of adherens junctions that regulates cell shape and maintains tissue integrity. A complete loss or any decrease in cell surface expression of E-cadherin will interfere with the cell-to-cell junctions' strength and leads to cell detachment and escape from the primary tumor site. In this prospective study, three functional single nucleotide polymorphisms (-347G/GA, rs5030625; -160C/A, rs16260; +54C/T, rs1801026), were found to modulate E-cadherin expression. Methods: 577 DNA samples from breast cancer (BC) cases were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results: We detected no significant correlations between each polymorphism and the clinical parameters of the patients whereas the GACC haplotype was significantly associated with low SBR grading. Overall survival analysis showed that both -347G/G and +54C/C wild (wt) genotypes had a significantly worse effect compared to the other genotypes (non-wt). Moreover, carrying simultaneously both the -347 and +54 wt genotypes confers a significantly higher risk of death. However, with metastatic recurrence, the death-rate was null in patients carrying the non-wt genotypes, and attained 37% in those carrying the wt genotype. A multivariate analysis showed that these two polymorphisms are independent prognostic factors for overall survival in BC patients. Conclusions: Our results support the fact that E-cadherin genetic variants control disease severity and progression and could be a marker of disease outcome. These findings could be useful in selecting patients that should be monitored differently.

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