Evaluation of miRNA-9 and miRNA-34a as potential biomarkers for diagnosis of breast cancer in Iranian women.

PURPOSE: MicroRNAs are involved in diverse biological processes and their dysregulation is a common event in various diseases including breast cancer. Breast cancer is a major threat to women's health. This study was designed to examine the expression levels of miR-9 and miR-34a in breast tumor tissue samples and plasma of breast cancer patients, compare their expression pattern between tissue samples and plasma samples of patients and analyze their relationship with tumor clinical features. Also, the potential of these miRNAs as diagnostic biomarkers for breast cancer was investigated.

MATERIALS AND METHODS: The expression levels of miR-9, miR-34a and CDH1 were measured by real-time reverse transcription polymerase chain reaction and ΔΔct method. Data were analyzed using t-test and one-way ANOVA. The sensitivity and specificity of miRNAs were determined by receiver operating characteristic (ROC) curve.

RESULTS AND DISCUSSION: The expression levels of miR-9 and miR-34a were significantly down-regulated in tumor tissues compared to healthy tissues (fold change = 0.26, p = 0.0051 for miR-9 and fold change = 0.55, p = 0.021 for miR-34a). While no significant difference was observed in the expression levels of miR-9 (p = 0.205) and miR-34a (p = 0.132) in plasma samples of patients compared to normal plasma. CDH1 expression in tumor tissue was not significantly different from normal tissue (p = 0.33). We found that expression level of miR-9 in patients with tumor size larger than 5 cm (p = 0.026) and expression level of miR-34a in patients with higher stage (lll & lV, p = 0.03) were significantly down-regulated. Also miR-34a expression level was positively correlated with patient's age (p = 0.03).

CONCLUSION: According to the ROC curves, the area under the curve (AUC) of miR-9 in tissue was 0.71 (p = 0.009) with sensitivity 83.33% and specificity 70.37%. The AUC for miR-34a in tissue was 0.72 (p = 0.007) with sensitivity 72% and specificity 76%. Thus miR-9 and miR-34a have the capability for distinguishing tumor tissues from healthy tissues and the study of their expression levels in tissue may be used as a biomarker for the diagnosis of breast cancer patients from healthy women.