Abstract
Deregulated expression of microRNAs has the oncogenic or tumor suppressor function in cancer. Since miRNAs in plasma are highly stable, their quantification could contribute to more precise cancer diagnosis, prognosis and therapy prediction. We have quantified expression of seven oncomiRs, namely miR-17/92 cluster (miR-17, miR-18a, miR-19a and miR-20a), miR-21, miR-27a and miR-155, in plasma of 137 breast cancer (BC) patients. We detected down-regulation of six miRNAs in patients with invasive BC compared to controls; however, only miR-20a and miR-27a down-regulations were statistically significant. Comparing miRNA expression between early and advanced stages of BC, we observed statistically significant decrease of miR-17 and miR-19a. We identified down-regulation of miR-17 and miR-20a in patients with clinical parameters of advanced BC (lymph node metastasis, tumor grade 3, circulating tumor cells, higher Ki-67-related proliferation, hormone receptor negativity and HER2 amplification), when compared to controls. Moreover, decreased level of miR-17 was found from low to high grade. Therefore, miR-17 could represent an indicator of advanced BC. Down-regulated miR-27a expression levels were observed in all clinical categories regardless of tumor progression. Hence, miR-27a could be used as a potential diagnostic marker for BC. Our data indicates that any changes in miRNA expression levels in BC patients in comparison to controls could be highly useful for cancer-associated pathology discrimination. Moreover, dynamics of miRNA expression changes could be used for BC progression monitoring.
Highlights
Breast cancer (BC) is the most common female malignancy
We found significantly decreased levels of miR-20a in patients with invasive breast cancer (BC) compared to healthy controls and lower levels of miR-17 and miR19a in invasive than in non-invasive BC
It has been documented that miRNAs located within miR-17/92 cluster are integrated in many essential biological process
Summary
Breast cancer (BC) is the most common female malignancy. In 2012, there have been almost 1.68 million new BC cases and 0.52 million BC deaths worldwide representing 25.2% and 14.7% of all cancers diagnosed in women, respectively [1]. Targeted down-regulation of the AIB1 gene (amplified in breast cancer 1) expression by miR-17-5p has been shown to result in decreased cell proliferation, indicating a possible tumor suppressor role of this miRNA in breast tumorigenesis. It has been documented that miR-27a may activate Wnt/β-catenin signaling pathway by negative regulation of SFRP1 (secreted frizzled related protein 1) affecting proliferation, migration and invasion of BC cells This observation was supported by detection of higher miR27a expression and lower SFRP1 mRNA and protein expression in BC when compared to normal breast tissues [31]. Significantly higher miR-155 expression was detected in both sub-groups compared to healthy controls, indicating association of increased miR155 plasma levels with tumor progression [44]. MiR-17 down-regulation has been associated with high tumor grade in contrast to miR-27a, which we observed to be down-regulated in all evaluated clinical categories regardless of tumor progression
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