Abstract
Oncogenic microRNAs (oncomiRs) accumulate in serum due to their increased stability and thus serve as biomarkers in breast cancer (BC) pathogenesis. Four oncogenic microRNAs (miR-155, miR-19a, miR-181b, and miR-24) and one tumor suppressor microRNA (let-7a) were shown to differentiate between high- and low-risk early breast cancer (EBC) and reflect the surgical tumor removal and adjuvant therapy. Here we applied the longitudinal multivariate data analyses to stochastically model the serum levels of each of the oncomiRs using the RT-PCR measurements in the EBC patients (N = 133) that were followed up 4 years after diagnosis. This study identifies that two of the studied oncomiRs, miR-155 and miR-24, are highly predictive of EBC relapse. Furthermore, combining the oncomiR level with Ki-67 expression further specifies the relapse probability. Our data move further the notion that oncomiRs in serum enable not only monitoring of EBC but also are a very useful tool for predicting relapse independently of any other currently analyzed characteristics in EBC patients. Our approach can be translated into medical practice to estimate individual relapse risk of EBC patients.
Highlights
Breast cancer (EBC) represents an early stage tumorous process defined as a breast cancer (BC) that has not spread beyond the breast or the axillary lymph nodes that can progress into a deadly disseminated cancer
OncomiRs miR-155 and miR-24 Are Predictive of Early Breast Cancer (EBC) Relapse
The multivariate generalized estimating equations (GEE) model revealed that miR-155 and miR-24 were predictive of the Early breast cancer (EBC) relapse (p-values 0.025 and 0.041, respectively)
Summary
Breast cancer (EBC) represents an early stage tumorous process defined as a breast cancer (BC) (including ductal carcinoma in situ and invasive BC stages I, IIA, IIB and IIIA) that has not spread beyond the breast or the axillary lymph nodes that can progress into a deadly disseminated cancer. MicroRNAs appear as very promising tumor biomarkers [1], mostly because they are highly resistant against degradation in many different tissues and body fluids, are easy to determine, and most importantly, their level is often a measure of the tumor burden associated with other clinically relevant characteristics of the oncogenic process. Circulating microRNAs are 18–24 nt long non-coding RNAs that are present in the serum or plasma as a result of higher turnover from the malignant cells [2]. Within these cells microRNAs bind mRNA molecules and inhibit gene expression by posttranscriptional mechanisms involving degradation of mRNA and inhibition of translation
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