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Small non-coding RNA profiling in breast cancer: plasma U6 snRNA, miR-451a and miR-548b-5p as novel diagnostic and prognostic biomarkers

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Abstract

Background

Breast cancer is a leading cause of cancer-related death in women. Most cases are invasive ductal carcinomas of no special type (NST breast carcinomas).

Methods and Results

In this prospective, multicentric biomarker discovery study, we analyzed the expression of small non-coding RNAs (mainly microRNAs) in plasma by qPCR and evaluated their association with NST breast cancer. Large-scale expression profiling and subsequent validations have been performed in patient and control groups and compared with clinicopathological data. Small nuclear U6 snRNA, miR-548b-5p and miR-451a have been identified as candidate biomarkers. U6 snRNA was remarkably overexpressed in all the validations, miR-548b-5p levels were generally elevated and miR-451a expression was mostly downregulated in breast cancer groups. Combined U6 snRNA/miR-548b-5p signature demonstrated the best diagnostic performance based on the ROC curve analysis with AUC of 0.813, sensitivity 73.1% and specificity 82.6%. There was a trend towards increased expression of both miR-548b-5p and U6 snRNA in more advanced stages. Further, increased miR-548b-5p levels have been partially associated with higher grades, multifocality, Ki-67 positivity, and luminal B rather than luminal A samples. On the other hand, an association has been observed between high miR-451a expression and progesterone receptor positivity, lower grade, unifocal samples, Ki-67-negativity, luminal A rather than luminal B samples as well as improved progression-free survival and overall survival.

Conclusions

Our results indicated that U6 snRNA and miR-548b-5p may have pro-oncogenic functions, while miR-451a may act as tumor suppressor in breast cancer.

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Acknowledgements

We appreciate the support of this research by Charles University in Prague (Progres Q28/LF1, Progres Q25/LF1), Ministry of Health of the Czech Republic (CZ-DRO FNBr 65269705, RVO-VFN 64165), Avast Foundation (SSD2018\100022) and ČEPS a.s. (1410002640, 1410002385, 1410002088). We would like to thank Libor Viktora, M.D. for clinicopathological data assessment (Center I data).

Funding

LZ received institutional funding from Charles University, Prague (Progres Q28/LF1) and research support from the Avast Foundation (SSD2018\100022) and ČEPS a.s. (1410002640, 1410002385, 1410002088). OS received institutional funding from Charles University, Prague (Progres Q25/LF1). AH received institutional funding from Charles University, Prague (Progres Q25/LF1) and research support from the Ministry of Health of the Czech Republic (Grant Project RVO-VFN 64165). VW and LM received research support from the Ministry of Health of the Czech Republic (CZ-DRO FNBr 65269705). MK received institutional funding from Charles University, Prague (Progres Q28/LF1).

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Authors and Affiliations

  1. Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University, Prague and General University Hospital in Prague, Albertov 4, 128 00, Prague, Czech Republic

    Luděk Záveský, Aleš Hořínek & Milada Kohoutová

  2. Institute of Pharmacology, First Faculty of Medicine, Charles University, Prague and General University Hospital in Prague, Albertov 4, 128 00, Prague, Czech Republic

    Luděk Záveský & Ondřej Slanař

  3. Department of Pathology, Faculty of Medicine, Masaryk University and University Hospital Brno, Obilní trh 11, 602 00, Brno, Czech Republic

    Eva Jandáková

  4. Department of Obstetrics and Gynecology, Masaryk University and University Hospital Brno, Obilní trh 11, 602 00, Brno, Czech Republic

    Vít Weinberger & Luboš Minář

  5. Faculty Transfusion Center, General University Hospital in Prague, U Nemocnice 2, 128 08, Prague, Czech Republic

    Veronika Hanzíková & Daniela Dušková

  6. Institute for Mother and Child Care, Podolské nábřeží 157/36, 147 00, Prague - Podolí, Czech Republic

    Adéla Faridová & Radovan Turyna

  7. 3rd Department of Medicine, Department of Endocrinology and Metabolism, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague 2, Czech Republic

    Aleš Hořínek

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Záveský, L., Jandáková, E., Weinberger, V. et al. Small non-coding RNA profiling in breast cancer: plasma U6 snRNA, miR-451a and miR-548b-5p as novel diagnostic and prognostic biomarkers. Mol Biol Rep 49, 1955–1971 (2022). https://doi.org/10.1007/s11033-021-07010-8

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