Introduction/Background Various tumor types including breast cancer (BC) are known to have specific microRNA (miR) expression profiles. This work was initially designed to identify microRNAs which are characteristic for hereditary BCs arising in BRCA1, CHEK2, NBS1 or BLM germ-line mutation carriers.
Methodology Small RNA profiling was performed by the next generation sequencing (NGS). 11 BRCA1-, 9 CHEK2-, 7 NBS1-, 3 BLM-associated and 16 sporadic fresh-frozen BCs were investigated with the use of NEXTFlex Small RNA Seq Kit (Bioo Scientific) on Illumina NextSeq500 platform.
Results Comparison of different categories of hereditary breast cancer with sporadic tumors did not identify unique miRNAs or specific expression profiles characteristic for BRCA1-, CHEK2-, NBS1- or BLM-dependent BC. However, the analysis of sequencing data revealed that expression of 51, 16, 125, and 168 miRNAs was associated with the ER-status, PR-status, patients‘ age, and Ki67 proliferation index, respectively. The most significant differences were observed for miR-190b-5p: its expression was extremely low or completely absent in all ER-negative tumors and, conversely, high in ER-positive tumors (p=1.43E-59). This microRNA can be a valuable marker for validation of the tumor ER status. The mechanisms underlying differential expression of miR-190b-5p in hormone-dependent and -independent breast cancer remain unclear.
Conclusion Hereditary and sporadic breast carcinomas are similar in terms of microRNA expression patterns. A single microRNA, miR-190b-5p, is capable to very reliably discriminate between ER-positive and ER-negative tumors. This finding is of practical importance: ER status determination still remains a manual and somewhat subjective procedure, while microRNA expression measurement can be performed in a semi-automated way and is not prone to inter-observer variations.
Disclosure This work has been supported by the Russian Science Foundation (grant number 17-15-01384).
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