Non-invasive biomarkers for breast cancer detection

Shiva Shariati,1,* Elahe ferdosi shahandashti,2

1. Department of Medical biotechnology, Faculty of Medicine, Babol university of Medical sciences
2. Department of Medical biotechnology, Faculty of Medicine, Babol university of Medical sciences

Abstract

Introduction

Breast cancer is one of the most common cancer among women, it is estimated that each year 1.5 million people are affected. nowadays, with the improvement of the standard techniques in the diagnosis of breast cancer, we are witnessing a decline in the death rate of affected people. two of these commonly used techniques for diagnosing breast cancer in the world are mammography and biopsy of the tumor tissue. x-rays from a mammogram in young women with brca gene mutations that require screening at age 30 can lead to breast cancer and also because of high breast tissue densities in young women, this technique is not effective. in fact, mammography has a low sensitivity and specificity that increases the error rate in the diagnosis (false positives 19% and false negatives 17%). biopsy of the tumor tissue is an invasive method for diagnosis, so some people refuse to do because of fear of pain. thus, according to conducted studies non-invasive, accurate and specific method for early detection of breast cancer, is necessary which blood analysis and identifing biomarkers is one of these methods. the 19-22 nucleotide microrna, are highly protected single strands that contribute to cell proliferation, angiogenesis, metastasis, tumorigenesis, apoptosis and the like. recently, it has been shown that circularting microrna released from many apoptotic and necrotic cells, so these micrornas are visible in many biological fluid (blood, urine, saliva, ...). encapsulated in the microvesicles or exosomes, binding to proteins (npm1) , lipoproteins (hdl, ldl)and ago2 cause them stable against, rnases , ph changes and more. therefore, their persistence in biological fluids, including (blood and serum, …)can be a non-invasive biomarker with high specificity and sensitivity in early diagnosis of breast cancer. some of these circulating microrna in the initial stage are dysregulated, that can be used for diagnosis before doing any biopsy, imaging and clinical signs.a number of these circulating microrna (mir1202-5p, mir1207-5p, mir1225-5p, mir4270-5p, mir4225-5p), that have been increased in the plasma of patients at stage Ι of breast cancer, have been presented as a diagnostic panel. in another study, over expression (mir-96-5p, mir505-5p, mir125-5p) in plasma was expressed as biomarkers for non-invasive breast cancer detection.

Methods

Different methods are used to identify circulating microrna in blood, plasma and ... samples. q-rt-pcr is the most widely used technique, which has high sensitivity, accuracy and dynamic range, and the most oftenly is used to evaluate the quantity level of microrna, which takes about 6 hours. microarray is a technique of moderate complexity, but its precision and dynamic range are less than other techniques and cannot detect novel circulating microrna. the input of the rna is low for its analysis and duration of performance is about 1 to 2 days. ngs technique can be used to identify known and novel microrna and is highly accurate. ngs has a complex system and requires computational analysis and cannot detect more than 800 microrna in each sample, it also takes 1 to 2 weeks. sample type and extraction techniques: the extraction of rna from a biological fluids samples is the first step in using the above techniques . serum and plasma are the most common types of samples used in the detection of circulating microrna in breast cancer. by examining these microrna, it has been shown that serum is less susceptible to hemolysis so is a better sample than plasma . due to the binding of these microrna to proteins, apoptotic bodies or exosomes, the chosing of a standard method for extraction can play a key role in the identification of all the presented microrna in the sample

Results

in studies conducted so far, circulating microrna have difference expression in breast cancer patients compared to control groups, but the provided diagnostic panels, due to differences in type and amount of samples, inappropriate statistical analysis, different methods for extraction and effect simultaneous illnesses on circulating microrna are seen to be less overlapping between the presented panels.

Conclusion

Circulating microrna can be used as precise, specific and non- invasive biomarkers for early diagnosis of breast cancer. therefore, the need for more extensive studies as well as the use of standardized guidelines are required to perform

Keywords

Breast cancer, biomarkers, circulating microrna