الفهرس 
Review of LiteratureOnly 14 pages are availabe for public view
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Abstract
Breast cancer is the most commonly diagnosed cancer in women worldwide and the principal cause of cancer related mortality. In Egypt, the incidence of breast cancer ranks second after liver cancer.
MicroRNAs (miRs) are endogenous short noncoding transcripts that play important gene-regulatory roles. MiRs act as potential oncogenes (oncomiRs) or tumor suppressors (tsmiRs) and their altered expression in biological fluids was linked to the existence of many cancers, including breast cancer.
To improve the treatment quality and the survivability rate of breast cancer patients, high accuracy in the early detection is crucial. Accordingly, this study aimed at analyzing the expression of a panel of some circulating oncomiRs and tsmiRs, including miR-10b, miR-21, miR-145, miR-155, miR-181a, and let-7a, as non-invasive molecular biomarkers for the initial detection of locally advanced breast cancer (LABC) patients, treatment response, and predicting relapse or metastasis.
The study comprised 30 female LABC patients and 20 healthy female subjects. Three blood samples were collected from LABC patients (pre-, inter- and post-treatments). The change in the level of candidate plasma miRs was evaluated. Serum CEA and CA 15-3 levels were determined using ELISA. The expressions of selected miRs were evaluated by quantitative real-time PCR analysis.
The obtained results are summarized as follows:
• A significant up-regulation in the expression of miR-10b, miR-21 and miR-181a levels was recorded, along with a significant increase in CA 15-3 and CEA levels in Pre-LABC patients, whereas a significant down-regulation was demonstrated in the expression of miR-145 and let-7a, compared to healthy controls.
• A gradual significant decrease was recorded in miR-10b and miR-21 expression levels, as well as the tumor size, whereas a gradual significant increase in let-7a level was demonstrated among the different treatment stages of LABC patients.
• A non-significant change was recorded in miR-145 and miR-181a, as well as serum CA 15-3 and CEA levels for inter-LABC patients, compared to pre-treatment, whereas a significant increase was recorded in miR-145 level, while miR-181a, CA 15-3 and CEA levels were significantly decreased in post-LABC patients, compared to pre- and inter-LABC patients. All candidate miRs rebound to the control values by the end of the treatment and breast tumor resection.
• Absolute specificity values were recorded for both miR-10b and miR-21, whereas the highest diagnostic accuracy was recorded for miR-21 for LABC patients at initial diagnosis.
• In pre-LABC patients, significant positive correlations between oncomiRs (miR-10b and miR-21) and clinicopathological data (CA 15-3 and tumor size) were recorded, while significant negative correlations were obtained between tsmiRs (miR-145 and let-7a) and oncomiRs (miR-10b and miR-21) and clinicopathological data (CA 15-3 and tumor size).
• Using the cut-off values of miR-10b and miR-21, it was possible to significantly sort out breast cancer patients who were free from cancer relapse or metastasis, out of breast cancer patients who suffered from breast tumor relapse and metastases.
In conclusion, the expression levels of candidate plasma miRs can be used as useful diagnostic biomarkers, as well as monitoring a proper response for LABC patients to the treatment. MiR-10b and miR-21 can be considered as predictive biomarkers for disease-free survival.