Circulating microRNAs in plasma as early detection markers for breast cancer

Abstract

In recent years, circulating miRNAs have attracted a great deal of attention as promising novel markers for various diseases. Here, we investigated their potential to serve as minimally invasive, early detection markers for breast cancer in blood plasma. We profiled miRNAs extracted from the plasma of early stage breast cancer patients (taken at the time-point of diagnosis) and healthy control individuals using TaqMan low-density arrays (TLDA). Selected candidates identified in the initial screen were further validated in an extended study cohort of 207 individuals including 127 sporadic breast cancer cases and 80 healthy controls via RT-qPCR. Four miRNAs (miR-148b, miR-376c, miR-409-3p and miR-801) were shown to be significantly upregulated in the plasma of breast cancer patients. ROC curve analysis showed that the combination of only three miRNAs (miR-148b, miR-409-3p and miR-801) had an equal discriminatory power between breast cancer cases and healthy controls as all four miRNAs together (AUC 5 0.69). In conclusion, the identified miRNAs might be of potential use in the development of a multimarker blood-based test to complement and improve early detection of breast cancer. Such a multimarker blood test might for instance provide a prescreening tool, especially for younger women, to facilitate decisions about which individuals to recommend for further diagnostic tests.Breast cancer is the most common type of cancer and cause of cancer-related death among women in industrialized countries. Worldwide $ 1.3 million women develop breast cancer each year.1 Mortality rates have continued to decrease over the years due to the advances made in early diagnosis and treatment.1 Nevertheless, thousands of women die from this disease each year. In the United States, the overall 5-year survival is 98% when diagnosed at an early stage as opposed to 23% when the disease has already spread to distant organs.

Analysis of circulating microRNAs in adrenocortical tumors

“…Moreover, previous reports described RNU6B as having unstable expression and tendency to degradation in plasma/serum samples. 18,21 Indeed, in our study, we also observed RNU6B instability in several samples. Other studies applied synthetic exogenous RNA molecules (cel-miR-39, cel-miR-54 and celmiR-238) as reference genes.…”

“…12 Recent findings have raised the potential applicability of circulating miRNAs as markers of malignancy in tumors of different organs. [20][21][22][23][24] Regarding the significant differences in tissue miRNA expression in ACTs reported in several independent studies, we hypothesized that circulating miRNAs might also be differentially expressed in benign and malignant ACTs and might serve as potential minimally invasive biomarkers of malignancy. Technical problems associated with the analysis of circulating miRNAs have also been addressed in our study.…”

Usefulness of miRNA profiles for predicting pathological responses to neoadjuvant chemotherapy in patients with human epidermal growth factor receptor 2-positive breast cancer

“…Furthermore, differential miRNA expression was separately examined according to the luminal B-like (HER2-positive) and HER2-positive (non luminal) subtypes. For the luminal B-like (HER2-positive) subtype, 17 miRNAs were differentially expressed (Table IV), and nine of these 17 miRNAs are reported to be correlated with breast cancer (20)(21)(22)24,(26)(27)(28)(29)(30). For the HER2-positive (non luminal) subtype, 14 miRNAs were differentially expressed (Table V), and five of these are reported to be correlated with breast cancer (17,23,25,31,32).…”

P1–234: Circulating miRNA biomarkers for Alzheimer's disease

“…Due to the nature of circulating fluids being the common reservoir for all secreted molecules from all organs and tissues, the candidate miRNA biomarker could be involved in diseases of various other organs, hence making the correlation harder. Also, higher expression of a miRNA in an affected organ is not necessarily accompanied by an increase in its plasma level, as was previously shown [66] [67]. In a related approach, instead of focusing on the disease etiology, some studies have focused on a selected panel of miRNAs, which were determined to be enriched in brain and neurons [68], thus increasing the likelihood that any changes in plasma or serum is a result of changes in neurons versus other organs.…”