Abstract. The purpose of the present study was to investigate the serum levels of microRNA (miRNA/miR)-382-3p, -598-3p, -1246 and -184 in breast cancer patients and to assess their feasibility as biomarkers for breast cancer screening. Serum samples were obtained from 100 breast cancer patients and 40 age-matched healthy control subjects in Taizhou Central Hospital (Taizhou, Zhejiang, China) between January 2013 and September 2014. The serum expression levels of miR-382-3p, -598-3p, -1246 and -184 were determined by stem-loop reverse transcription-quantitative polymerase chain reaction. Receiver operating characteristic curves were drawn to evaluate the sensitivity and specificity of the serum miRNA expression levels for the screening of breast cancer. miR-382-3p and -1246 were significantly upregulated in the serum of the breast cancer patients, while miR-598-3p and -184 were significantly downregulated. The sensitivity and specificity to detect breast cancer were as follows: miR-382-3p, 52.0 and 92.5%; miR-598-3p, 95.0 and 85.0%; miR-1246, 93.0 and 75.0%; and miR-184, 87.5 and 71.0%, respectively. The expression levels of the four serum miRNAs were not correlated with the patients' clinical stage. In summary, miR-382-3p, -598-3p, -1246 and -184 are all involved in the development of breast cancer, and are promising biomarkers for breast cancer detection.
IntroductionBreast cancer has become the most common cancer in women in China, accounting for 12.2% of all newly diagnosed breast cancers and 9.6% of all mortalities from breast cancer worldwide (1). Early detection of breast cancer is the key to successful treatment and patient survival. Mammographies, magnetic resonance imaging and ultrasound are being used for the screening of breast cancer, but these techniques have limitations such as low sensitivity and specificity (2). Finding effective biomarkers is vital for the screening of breast cancer.MicroRNAs (miRNAs/miRs) are a group of small non-coding RNAs (3), which can bind to the 3' untranslated region (UTR), the 5' UTR (4) or the coding region (5) of target mRNA. miRNAs play important roles in the negative regulation of gene expression in a post-transcriptional manner, and are involved in a number of signal transduction pathways, including cell proliferation, differentiation, apoptosis, immune response and angiogenesis (6). Previous studies have revealed the abnormal expression of miRNAs in the development and progression of breast cancer (7), and miRNAs are closely linked with tumor-associated signal transduction pathways (8). In our previous study, 10 miRNAs that were significantly differentially expressed were found by the second generation of high-throughput sequencing technology, Illumina Hiseq2500 (9). In the present study, 4 miRNAs, miR-382-3p, -598-3p, -1246 and -184, were further investigated. The purpose of this study was to investigate the serum levels of these miRNAs in breast cancer patients and to assess their feasibility as biomarkers for breast cancer screening.
Materials and methods
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