Abstract
Over the last few years, circulating microRNAs (miRNAs) have emerged as promising novel and minimally invasive markers for various diseases, including cancer. We already showed that certain miRNAs are deregulated in the plasma of breast cancer patients when compared to healthy women. Herein we have further explored their potential to serve as breast cancer early detection markers in blood plasma. Circulating miR-127-3p, miR-376a and miR-652, selected as candidates from a miRNA array-based screening, were found to be associated with breast cancer for the first time (n = 417). Further we validated our previously reported circulating miRNAs (miR-148b, miR-376c, miR-409-3p and miR-801) in an independent cohort (n = 210) as elevated in the plasma of breast cancer patients compared to healthy women. We described, for the first time in breast cancer, an over-representation of deregulated miRNAs (miR-127-3p, miR-376a, miR-376c and miR-409-3p) originating from the chromosome 14q32 region. The inclusion of patients with benign breast tumors enabled the observation that miR-148b, miR-652 and miR-801 levels are even elevated in the plasma of women with benign tumors when compared to healthy controls. Furthermore, an analysis of samples stratified by cancer stage demonstrated that miR-127-3p, miR-148b, miR-409-3p, miR-652 and miR-801 can detect also stage I or stage II breast cancer thus making them attractive candidates for early detection. Finally, ROC curve analysis showed that a panel of these seven circulating miRNAs has substantial diagnostic potential with an AUC of 0.81 for the detection of benign and malignant breast tumors, which further increased to 0.86 in younger women (up to 50 years of age).
Highlights
Breast cancer is the most common type of cancer and the leading cause of cancer-related death among women in industrialized countries
We have conducted an initial screening using TaqMan Low Density (TLDA) arrays to identify circulating miRNAs deregulated between early stage breast cancer patients and healthy controls (Table S2 and [12])
First we measured the miRNA levels of miR-127-3p, miR-376a and miR-652 in study cohort A (n = 207), comprising a total of 127 breast cancer patients and 80 healthy controls
Summary
Breast cancer is the most common type of cancer and the leading cause of cancer-related death among women in industrialized countries. Worldwide approximately 1.3 million women develop breast cancer each year [1]. Tens of thousands of women die from breast cancer each year. Mammography is the standard breast cancer screening tool, but there are controversial reports regarding its utility as a screening method [3,4]. Mammographic screening seems to be less sensitive for younger women, possibly due to an increased mammographic breast density, which is usually associated with younger age [5,6]. As of there are no circulating markers for breast cancer screening or detection in clinical use, but a few such
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