Aberrant Expression of Micro RNA for Diagnosis of Breast Cancer

Aberrant Expression of Circulating Micro RNA as a Biomarker for Diagnosis of Breast Cancer in Egyptian Females

In this study we aim to:

1. Assess serum miRNA-373, miRNA-425-5p expression in patients with breast cancer.
2. Explore their correlations with breast cancer clinicopathological documented data including staging, grading and tumor receptors.

Breast cancer (BC) is the leading cause of cancer worldwide with estimated 2.3 million new cases and 685000 deaths in 2020. In women, breast cancer accounts for one in 4 cancer cases and one in 6 cancer deaths.

In Egypt, BC is the most common cancer among females accounting for 32.0% of all cancers in women according to the data of the National Cancer Registry Program of Egypt . 22038 Egyptian females breast cancer new cases were estimated to be in 2020 .

The most important risk factors for breast cancer include female gender, age (30 years old and older), positive family history for breast cancer , and familial genetic mutations, including mutations in the breast cancer A1 (BRCA1) and BRCA2 genes. Furthermore, women with a history of breast cancer are more likely (20-25%) to develop microscopic cancer in the opposite breast. A positive history for cancer in the endometrium, ovaries, or colon, as well as radiation therapy for Hodgkin's lymphoma, was shown to increase the risk of breast cancer.

The gold standard for diagnosis of breast cancer is histopathology. Several tumor markers have been suggested for the evaluation and management of breast cancer including estrogen and progesterone receptors (ER/PR), which are used for the assessment of susceptibility to hormone treatment, and human epidermal growth factor receptor 2 (HER2), which is used to assess the susceptibility to trastuzumab treatment.

With the rapid development of medical technology, strategies such as surgery, medication and radiotherapy can help a lot to reduce mortality rate. Though clinical intervention at early stage can greatly improve prognosis, many BC patients are asymptomatic until disease progression.

Thus, effective screening methods are in great demand for the early detection of BC. In clinical practice, many screening strategies have been widely used, such as mammography, breast magnetic resonance imaging (MRI) and ultrasound imaging.

However, these strategies are far from being perfect because of over-diagnosis, false-positive inconsistent results and potential radiation injury.

Core needle aspiration can help establish the diagnosis, but the procedure is invasive and not suitable for routine use .

Therefore, novel non-invasive screening methods of high sensitivity and specificity are needed to assist the early diagnosis of BC .

Microribonucleic Acids (microRNAs) are a large subgroup of noncoding RNAs made up of 18-25 nucleotides. MicroRNAs regulate gene expression after transcription. They have a multifunctional role, as they can perform either as oncogenes by repressing their target tumor suppressor genes, or as tumor suppressors through inhibiting the expression of their target oncogenes.

Numerous studies have shown that miRNAs played important roles in nearly all biological processes and their aberrant expression was associated with many diseases including cancers. Stable existence of miRNAs in peripheral blood circulation revealed that they could be promising noninvasive biomarkers for cancer detection.

For BC, more and more circulating miRNAs (ie, miRNA-373, miRNA-425-5p) are emerging as potential diagnostic or prognostic biomarkers.

In breast cancer miRNA-425-5p was found elevated and predicted a poor prognosis for the patients, and its role in BC highlight a new research points for diagnostic and therapeutic plans.

MiRNA-373 Circulating level has been reported as a potential biomarker of lymph node metastasis and its expression has been linked to promoting migration and invasion of breast cancer cells. It has also been reported that correlations between decreased miRNA-373 expression and BC relapse.

However, findings often differed from each other due to different experiment design, study cohorts or disease status.

Inclusion Criteria:

• Female age 20 years or older
• documented diagnosis of breast cancer based on physical examination, imaging and histopathology
• possibility of obtaining blood samples from the subject.

Exclusion Criteria:

• All patients with prior history of exposure to chemotherapy, radiotherapy or hormonal therapy .
• patients with other malignancies.
• patients with chronic inflammatory diseases.
• patients with missed documentation for histopathological diagnosis of breast cancer.