Abstract
Circulating microRNAs have drawn a great deal of attention as promising novel biomarkers for breast cancer. However, to date, the results are mixed. Here, we performed a three-stage microRNA analysis using plasma samples from breast cancer patients and healthy controls, with efforts taken to address several pitfalls in detection techniques and study design observed in previous studies. In the discovery phase with 122 Caucasian study subjects, we identified 43 microRNAs differentially expressed between breast cancer cases and healthy controls. When those microRNAs were compared with published data from other studies, we identified three microRNAs, including miR-148b, miR-133a and miR-409-3p, whose plasma levels were significantly higher in breast cancer cases than healthy controls and were also significant in previous independent studies. In the validation phase with 50 breast cancer cases and 50 healthy controls, we validated the associations with breast cancer detection for miR-148b and miR-133a (P = 1.5×10-6 and 1.3×10-10, respectively). In the in-vitro study phase, we found that both miR-148b and miR-133a were secreted from breast cancer cell lines, showing their secretory potential and possible tumor origin. Thus, our data suggest that both miR-148b and miR-133a have potential use as biomarkers for breast cancer detection.
Highlights
MicroRNAs are a class of small noncoding RNAs that play a central role in the regulation of mRNA expression [1-5]
The potential of circulating microRNAs as www.impactjournals.com/oncotarget biomarkers for cancer early detection is relevant to breast cancer because it is the most common cancer in US women, regardless of race or ethnicity, despite improvement in cancer screening and treatment strategies
The diagnosis of breast cancer relies on the histological examination of tissue biopsies, or cytology of fineneedle aspirates, which are both invasive procedures
Summary
MicroRNAs are a class of small noncoding RNAs that play a central role in the regulation of mRNA expression [1-5]. The discovery that microRNA expression is frequently dys-regulated in a cancer-specific manner provides an opportunity to develop these RNAs as biomarkers for cancer detection [6-12]. Most previous studies on microRNA expression have been performed on tissue specimens. The potential of circulating microRNAs as www.impactjournals.com/oncotarget biomarkers for cancer early detection is relevant to breast cancer because it is the most common cancer in US women, regardless of race or ethnicity, despite improvement in cancer screening and treatment strategies. The diagnosis of breast cancer relies on the histological examination of tissue biopsies, or cytology of fineneedle aspirates, which are both invasive procedures. Known serum-based tumor markers, such as CA15.3 and BR27.29, cannot be used for breast cancer detection due to low sensitivity. There is a need for developing novel markers that are minimally invasive, for the improved detection of breast cancer
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