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

Journal of Translational Medicine

Research

Karim Farhat¹  Lotfi Chouchane²  Wijden Mahfoudh³  Yassmine Remadi³  Sallouha Gabbouj³  Abdelfattah Zakhama⁴  Nadia Bouzid⁵  Noureddine Bouaouina⁵  Hager Memni⁶  Ahlem Ben-Haj-Ayed⁶  Yosra Macherki⁷  Zahra Klayech⁷  Elham Hassen⁷ 

[1] Cancer Research Chair, College of Medicine, King Saud University, Riyadh, Saudi Arabia;Laboratory of Genetic Medicine and Immunology, Weill Cornell Medicine-Qatar, Education City, Qatar Foundation, Doha, Qatar;Laboratory of Molecular Immuno-Oncology, Faculty of Medicine of Monastir, Monastir University, 5019, Monastir, Tunisia;Laboratory of Molecular Immuno-Oncology, Faculty of Medicine of Monastir, Monastir University, 5019, Monastir, Tunisia;Department of Anatomy and Pathologic Cytology, Fattouma Bourguiba University Hospital, Monastir University, Monastir, Tunisia;Laboratory of Molecular Immuno-Oncology, Faculty of Medicine of Monastir, Monastir University, 5019, Monastir, Tunisia;Department of Cancerology and Radiotherapy, Farhat Hached University Hospital, Sousse University, Sousse, Tunisia;Laboratory of Molecular Immuno-Oncology, Faculty of Medicine of Monastir, Monastir University, 5019, Monastir, Tunisia;Faculty of Sciences of Bizerte, Carthage University, Bizerte, Tunisia;Laboratory of Molecular Immuno-Oncology, Faculty of Medicine of Monastir, Monastir University, 5019, Monastir, Tunisia;Higher Institute of Biotechnology of Monastir, Monastir University, Monastir, Tunisia;

关键词: E-cadherin;    SNP;    Prognosis;    Breast cancer;   

DOI  :  10.1186/s12967-016-1077-4

 received in 2016-08-29, accepted in 2016-11-08,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundE-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.Methods577 DNA samples from breast cancer (BC) cases were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR–RFLP).ResultsWe 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.ConclusionsOur 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.

【 授权许可】

CC BY   
© The Author(s) 2016