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

ABSTRACT: 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.577 DNA samples from breast cancer (BC) cases were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).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.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.

SUBMITTER: Memni H

PROVIDER: S-EPMC5112645 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

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

Memni Hager H Macherki Yosra Y Klayech Zahra Z Ben-Haj-Ayed Ahlem A Farhat Karim K Remadi Yassmine Y Gabbouj Sallouha S Mahfoudh Wijden W Bouzid Nadia N Bouaouina Noureddine N Chouchane Lotfi L Zakhama Abdelfattah A Hassen Elham E

Journal of translational medicine 20161116 1

<h4>Background</h4>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 ...[more]

PMID: 27852262

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Project description:Objective:Klatskin tumors are rare, malignant tumors of the biliary system with a poor prognosis for patient survival. The current understanding of these tumors is limited to a small number of case reports or case series; therefore, we examined prognostic factors of this disease. Methods:A population cohort study was conducted in patients selected from the Surveillance, Epidemiology, and End Results (SEER) database with a Klatskin tumor that was histologically diagnosed between 2004 to 2014. Propensity-matching (PSM) analysis was performed to determine the overall survival (OS) among those with a Klatskin tumor (KCC), intrahepatic cholangiocarcinoma (ICCA), or hepatocellular carcinoma (HCC). The nomogram was based on 317 eligible Klatskin tumor patients and its predictive accuracy and discriminatory ability were determined using the concordance index (C-index). Results:Kaplan-Meier analysis showed that patients with Klatskin tumors had significantly worse overall survival rates (1-year OS = 26.2%, 2-year OS = 10.7%, 3-year OS = 3.4%) than those with intrahepatic cholangiocarcinoma (1-year OS = 62.2%, 2-year OS = 36.4%, 3-year OS = 19.1%, p < 0.001) or hepatocellular carcinoma (1-year OS = 72.4% , 2-year OS = 48.5%, 3-year OS = 36.2%, p < 0.001). A poor prognosis was also significantly associated with older age, higher grade, SEER historic stage, and lymph node metastasis. Local destruction of the tumor (HR = 0.635, 95% CI [0.421-0.956], p = 0.03) and surgery (HR = 0.434, 95% [CI 0.328-0.574], p < 0.001) were independent protective factors. Multivariate Cox analysis showed that older age, SEER historic stage, and lymph node metastases (HR = 1.468, 95% CI [1.008-2.139], p = 0.046) were independent prognostic factors of poor survival rates in Klatskin tumor patients, while cancer-directed surgery was an independent protective factor (HR = 0.555, 95% CI [0.316-0.977], p = 0.041). The prognostic and protective factors were included in the nomogram (C-index for survival = 0.651; 95% CI [0.607-0.695]). Conclusions:The Klatskin tumor group had poorer rates of OS and cancer-specific survival than the ICCA and HCC groups. Early detection and diagnosis were associated with a higher rate of OS in Klatskin tumor patients.

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

Publications

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

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