Study of Mirna-100 and Mirna-598 in Egyptian Females Patients With Breast Ductal Carcinoma

Abstract Background Breast cancer (BC) is the most frequently discovered cancer in women. MicroRNAs are non-invasive cancer biomarker, they function as potential oncogenes or tumor suppressors. Dysregulation of miR-100 was reported to be involved in tumor occurrence, development and drug resistance. Ribosome Biogenesis Regulator 1 Homolog (RRS1) a breast cancer oncogene, which inhibition increases apoptosis and reduce cell proliferation. RRS1 is a direct miR-598 target gene. Jagged canonical Notch ligand 1 (JAG1) discovered as target of miR-598 is upregulated in TNBC tissues and miR-598 level is downregulated in TNBC tissues. The expression pattern of miR-598 and miR-100 in breast cancer is not fully elucidated. The aim of the present work is to study miRNA-100 and miRNA-598 in Egyptian females with breast ductal carcinoma. miRNA-100 and miRNA-598 was correlated with histopathological and prognostic parameters. Methods 25 breast tissue biopsy samples were collected from 25 non pregnant female patients with histopathologically proved breast ductal carcinoma as Patients Group (Group1) and from the clearly defined safety margin from the same 25 patients as Controls (Group 2) to study miRNA-100 & miRNA-598. Quantitative real time polymerase chain reaction (qPCR) was performed for both miRNAs: miR-100 and miR-598. Relative expressions of tissue miRNA- 100 and miRNA-598 were calculated by using the comparative cycle threshold (CT) method (2 –ΔΔCT ), after normalization for the expression of endogenous control. Results There is statistically significant negative correlation between tissue expression level of miR-100 and only the tumor stage (p = 0.046). There is statistically significant correlation between miR-100 and miR-598 studied (p = 0.000). There is statistically significant decrease in level of both miR-100 and miR-598 when comparing cases to controls (p = 0.001) and (p = 0.002) respectively. Both miRNAs are downregulated in 84% of cases and upregulated in 16% of cases. ROC curve analysis represents that there was statistically significant diagnostic accuracy of miR-100 in discriminating between cases and controls (AUC = 0.74, p = 0.003). At the best cutoff = 1.1 miRNA has sensitivity 88% and specificity 72%, and there was statistically significant diagnostic accuracy of miR-598 in discriminating between cases and controls (AUC = 0.73, p = 0.005). At the best cutoff of miR-598 which is = 0.98 miR-598 has sensitivity 84% and specificity 72%. Agreement for both tissue miR-100 and miR-598 at their best cutoff = 1.1 and 0.98 respectively shows sensitivity 100%, specificity 68%, PPV 75%, NPV 100%. It is found that together tissue miR-100 and miR-598 below their best cutoff have better sensitivity and negative predictive value than each miRNA alone. Conclusions MicroRNAs blood markers in breast cancer being not absolutely conclusive directed researchers to use tumor tissue miRNAs. The studied miR-100 and miR-598 are decreased in tissues of breast cancer when compared to adjacent control tissues. The diagnostic biomarkers miR-100 and miR-598 are potential tumor suppressors. MicroRNA-100 is better than miR-598 as breast tumor marker regarding the sensitivity, PPV, NPV and accuracy but both have the same specificity. Combining both tissue miR-100 and miR-598 in breast cancer have better sensitivity and NPV than using each miRNA alone.