CDH1 (E-cadherin) expression independently affects clinical outcome in acute myeloid leukemia with normal cytogenetics.

ABSTRACT

BACKGROUND: Epithelial-mesenchymal transition (EMT) is a critical process which involves in tumor metastasis. As an important EMT marker gene, CDH1 (E-cadherin) expression and its clinical implication in acute myeloid leukemia (AML) remain largely elusive. METHODS: Real-time quantitative PCR (RQ-PCR) was carried out to examine CDH1 transcript level in 123 de novo AML patients and 34 controls. RESULTS: Compared with controls, CDH1 was significantly downregulated in AML (p<0.001). The median level of CDH1 expression divided total AML patients into CDH1 low-expressed (CDH11ow) and CDH1 high-expressed (CDH1high) groups. There were no significant differences between the two groups in age, peripheral blood cell counts, complete remission (CR) rate, and the distribution of FAB/WHO subtypes as well as karyotypes/karyotypic classifications (p>0.05). However, CDH11ow group tended to have a higher bone marrow (BM) blasts (p=0.093). The spearman correlation analysis further illustrated a trend towards a negative correlation between CDH1 expression level and BM blasts (r=-0.214, p=0.052). CDH1low group had a tendency towards a lower frequency of N/K-RAS mutations (p=0.094). Furthermore, CDH1low patients had markedly shorter overall survival (OS) time in cytogenetic normal AML (CN-AML) (p=0.019). Both univariate and multivariate analyses confirmed the prognostic value of CDH1 expression in CN-AML patients (p=0.027 and 0.033, respectively). CONCLUSIONS: CDH1 downregulation acted as an independent prognostic biomarker in CN-AML patients.