![]() | Only 14 pages are availabe for public view |
Abstract B reast cancer is the most common type of cancer among women. Its detection and treatment in early stages allow the decrease in morbidity and the increase in the survival rate. However, despite the advances and new strategies for combining surgical, radiotherapy and chemotherapy options, the percentage of patients developing metastases and progressing to advanced stages remains high. In this prospect, more reliable methods are needed for earlier detection of breast cancer replacing the common clinical methods to start early treatment. Serum tumor markers have been commonly used for the diagnosis of breast cancer as CA 15.3, CA 27.29 and steroid receptor status. Unfortunately, they provide unsatisfactory sensitivity and specificity for identifying early stage patients. Thus, the search for non-invasive biomarkers with higher sensitivity for early detection of breast cancer still remains a scientific challenge. Current evidence suggests that miRNAs dysregulation may affect some crucial biological processes of cells leading to tumor development. Their expression level is altered in various cancers exhibiting great potential in improving the diagnosis and prognosis of many cancers including breast cancer. One of which is miRNA-21 and its alterations have been shown to play critical roles in breast cancer. In this regard, our study aimed to assess circulating miRNA-21 in a group of breast cancer patients in order to evaluate its clinical utility in breast cancer. This may allow intervention at an early stage and may have its impact on the therapeutic regimens. This study was conducted on thirty (30) female patients with breast cancer (group I), who were recruited from the Surgery Department and Out-Patient Clinics at EL Demerdash Hospitals, Ain-Shams University. This group was further classified into two subgroups, subgroup (Ia) early stages breast cancer (stage I & II) and subgroup (Ib) advanced stages breast cancer (stage III & IV), according to TNM stage classification. Results of this group were compared to ten (10) apparently healthy age- matched individuals serving as a healthy control group (group II). All studied individuals were subjected to full history, clinical examination with special emphasis on breast examination and mammogram. For patients only, radiological investigations as bone scan, CT scan and/or MRI as well as breast biopsy were done for histopathological examination and steroid receptors study. Serum CA 15.3 assay and finally, miRNA-21 assay by qRT-PCR were done for all individuals. Although CA 15.3 is the most widely used circulating biomarker in monitoring patients with breast cancer, it has a variably low specificity and sensitivity as reported by many previous studies. Our study emphasizes the possible role of miRNA-21 expression levels in early diagnosis of breast cancer patients with a superior both sensitivity and specificity of 100% specially in comparison with CA 15.3 that displayed 70% sensitivity and 60% specificity at our best chosen cut-offs. Moreover, increasing expression levels of microRNA-21 can successfully differentiate between the four stages of breast cancer patients specially between early breast cancer stages (I, II) and advanced breast cancer stages (III, VI) with diagnostic sensitivity of 86.7% and specificity 100% meanwhile, CA 15.3 lacks this criterion as proven in our study. According to our study results, increasing miRNA-21 expression levels in breast cancer patients statistically vary with both positive and negative ER which gives it an additional value in evaluating the treatment regimens designed for the cancer breast patients as well as a prognostic value related to its relation with both estrogen and progesterone receptor status. A significant positive correlation between, CA 15.3and miRNA-21, was shown in breast cancer patients (group I). In conclusion, our study revealed that miRNA-21 levels are significantly higher in breast cancer patients compared to healthy subjects. Furthermore, we found that increased miRNA-21 expression levels correlated with progression of breast cancer stages. Our findings indicate that serum miRNA-21 may serve as a novel potential diagnostic and prognostic marker for recurrence and survival of breast cancer patients before resection. |