ABSTRACT
Acute myeloid leukemia (AML) is the most common type of acute leukemia in adults, it represents nearly 32% of all new cases of leukemia. This study aimed to evaluate the SNAI1 and ZEB1 genes expression in AML patients and determine their diagnostic and prognostic significance. We determined the expression of SNAI1 and ZEB1 genes and serum E-cadherin levels in early diagnosed patients with AML. Sixty early diagnosed AML patients and 20 healthy subjects were enrolled in this study, SNAI1 and ZEB1 genes expression was determined by Real-time PCR while E-Cadherin serum levels were determined by ELISA. The results of this study demonstrated that, all AML patients positively expressed the SNAI1 gene with fold change 2.6. While, the ZEB1 expression was positive in 56.7% of the patients with fold change 1.8. SNAI1 and ZEB1 genes were highly expressed in M5 subtype (FC = 13.8 and 9.3, respectively). On the other hand, serum E-cadherin concentrations of the AML patients showed decrease when compared with those of the control but the decrease was not reach to the significance level. The findings of this study suggest inclusion of SNAI1 and ZEB1 genes expression in the cluster of potential genetic biomarkers to be studied in AML cases as diagnostic and prognostic markers.
Subject(s)
Leukemia, Myeloid, Acute/genetics , Snail Family Transcription Factors/genetics , Zinc Finger E-box-Binding Homeobox 1/genetics , Adult , Antigens, CD/blood , Biomarkers, Tumor/biosynthesis , Biomarkers, Tumor/genetics , Cadherins/blood , Female , Humans , Leukemia, Myeloid, Acute/blood , Male , Middle Aged , Prognosis , Snail Family Transcription Factors/blood , Snail Family Transcription Factors/metabolism , Transcriptome , Zinc Finger E-box-Binding Homeobox 1/blood , Zinc Finger E-box-Binding Homeobox 1/metabolismABSTRACT
BACKGROUND/AIM: Circulating tumor cells (CTCs) comprise a heterogeneous population of cancer cells with different clinical and biological value. The aim of this study was to evaluate the prognostic value of CTCs with an epithelial-mesenchymal transition (EMT) phenotype in primary breast cancer (PBC) patients. PATIENTS AND METHODS: This study included 427 primary breast cancer patients. RNA extracted from CD45-depleted peripheral blood mononuclear cell (PBMCs) was evaluated for the expression of EMT transcription factors (TWIST1, SNAIL1, SLUG, ZEB1) by quantitative real time polymerase chain reaction (qRT-PCR). RESULTS: In total, CTC EMT was detected in 77 (18.0%) patients. Patients without detectable CTC EMT in peripheral blood had significantly longer disease-free survival than patients with detectable CTC EMT. The prognostic value of CTC EMT was demonstrated in all subgroups of patients. CONCLUSION: CTCs with an EMT phenotype have a prognostic value in primary breast cancer.
Subject(s)
Breast Neoplasms/pathology , Breast Neoplasms/therapy , Epithelial-Mesenchymal Transition , Neoplastic Cells, Circulating/pathology , Adolescent , Adult , Aged , Aged, 80 and over , Breast Neoplasms/blood , Breast Neoplasms/genetics , Case-Control Studies , Child , Child, Preschool , Disease-Free Survival , Female , Humans , Middle Aged , Neoplastic Cells, Circulating/metabolism , Nuclear Proteins/blood , Nuclear Proteins/genetics , Phenotype , Prospective Studies , Snail Family Transcription Factors/blood , Snail Family Transcription Factors/genetics , Time Factors , Twist-Related Protein 1/blood , Twist-Related Protein 1/genetics , Young Adult , Zinc Finger E-box-Binding Homeobox 1/blood , Zinc Finger E-box-Binding Homeobox 1/geneticsABSTRACT
The primary cause of breast cancerassociated mortality is the formation of distant metastasis. During the metastatic process, single tumor cells dissolve from the primary tumor site and undergo various changes in cell adhesion and motility properties. The tumor cells invade the blood stream and travel to different sites of the body, where they may initiate outgrowth. These cells are referred to as circulating tumor cells (CTCs). The process of changing cellular properties is known as epithelial to mesenchymal transition (EMT). As a different set of genes is upregulated during EMT, such genes may serve as marker genes for the detection of CTCs based on reverse transcriptionquantitative polymerase chain reaction (RTqPCR). Therefore, EMT and breast cancerrelated genes were selected as RTqPCR markers. These genes were tested for performance in a model system of blood samples from healthy donors, to which a number of various breast cancer cell lines were added. The genes with optimal performance were subsequently used in RTqPCR with 35 breast cancer patient samples. The genes which showed the highest and most consistent increase in gene expression with the increase in the number of cancer cell line cells added were CK19, Snail, FoxC2 and Twist. Following RTqPCR for all patient samples, two subgroups were arranged: One group in which all genes were downregulated and the second group with at least one gene indicated an upregulation of gene expression. Comparisons were made between the tumour characteristics from these two groups. Results suggested that carcinomas of the first group exhibited a less aggressive tumor biology compared with those in the second group. The present study indicated a novel RTqPCR based test for tumor malignancy.
