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

• Published in: Molecular biology reports Vol. 49; no. 3; pp. 1955 - 1971
• Main Authors: Záveský, Luděk, Jandáková, Eva, Weinberger, Vít, Minář, Luboš, Hanzíková, Veronika, Dušková, Daniela, Faridová, Adéla, Turyna, Radovan, Slanař, Ondřej, Hořínek, Aleš, Kohoutová, Milada
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer Netherlands 01-03-2022; Springer Nature B.V
• Subjects: Animal Anatomy; Animal Biochemistry; Biomarkers; Biomarkers, Tumor - genetics; Biomedical and Life Sciences; Breast cancer; Breast carcinoma; Breast Neoplasms - diagnosis; Breast Neoplasms - genetics; Breast Neoplasms - pathology; Female; Gene Expression Regulation, Neoplastic - genetics; Histology; Humans; Invasiveness; Life Sciences; MicroRNAs - metabolism; miRNA; Morphology; Non-coding RNA; Original Article; Progesterone; Prognosis; Prospective Studies; RNA, Small Nuclear; snRNA; Survival; Tumor suppressor genes; Tumors; miR-548b-5p; microRNA; Biomarker; Breast cancer; U6 snRNA; miR-451a
• ISSN: 0301-4851; 1573-4978
• DOI: 10.1007/s11033-021-07010-8

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.