PLASMA LEVELS OF SOME microRNA IN BREAST CANCER IN THE KAZAKH POPULATION
Authors:   Corresponding author, M. Aitkhozhin Institute of Molecular Biology and Biochemistry, Acting Head of Laboratory, eldarasher@mail.ru, https://orcid.org/0000-0002-2265-9717, Ashirbekov Y.Y. , Abaildayev A.O. ,   M. Aitkhozhin Institute of Molecular Biology and Biochemistry, Junior Researcher, armandj_92@mail.ru, https://orcid.org/0000-0002-1813-1338, Belkozhayev A.M. ,   M. Aitkhozhin Institute of Molecular Biology and Biochemistry, Junior Researcher, ayaz_jarkent@mail.ru, https://orcid.org/0000-0001-7429-4994, Sharipov K.O. ,   Doctor of Biological Sciences, Professor, M. Aitkhozhin Institute of Molecular Biology and Biochemistry, General Director, Chief Researcher, imbb-acad.kz@mail.ru, skamalidin@mail.ru, https://orcid.org/0000-0001-5946-5521, Aitkhozhina N.A. ,   Academician of the National Academy of Sciences of the Republic of Kazakhstan, Doctor of Biological Sciences, Professor, M. Aitkhozhin Institute of Molecular Biology and Biochemistry, Chief Researcher aytkhozhina.nagima@bk.ru, https://orcid.org/0000-0003-2507-6645
Published: December 2020

Breast cancer is the most common cancer among women worldwide. The use of mammography screening for women, in the age range the most at risk to breast cancer, has led to a significant reduction in mortality from this disease. However, mammography shows a significant number of false positives in women at a younger age. This problem indicates the need to find new reliable, minimally invasive and cheap biomarkers of breast cancer. The relevance of the research is determined by the fact that breast cancer in Kazakh women often develops at a young age. The aim of this study was to test the diagnostic value of six plasma miRNAs in Kazakh women. For this, using the quantitative PCR technique, we compared the levels of the miRNAs in the plasma of breast cancer patients (n = 27) and healthy controls (n = 33), as well as in the breast tumor and adjacent normal tissue (n = 28). Quantitative data were normalized relative to endogenous control miR-16-5p. Plasma concentrations of miR-145-5p, miR-191-5p, and miR-21-5p were significantly increased in patients compared to controls (P = 6.58e-7, 2.70e-5, and 0.049, respectively). The levels of miR-191-5p and miR-210-3p were significantly increased, while the level of miR-145-5p was significantly reduced in the tumor compared to normal tissue (1.88e-6, 6.56e-7 and 9.66e-4, respectively). To test the hypothesis of the secretory origin of the studied plasma miRNAs, we analyzed the correlation of miRNA levels in plasma, tumor, and healthy breast tissue. Correlation analysis showed that there may be a relationship between plasma and tumor levels of miR-145-5p. Plasma level of miR-210-3p correlated with tissue ∆∆Ct, plasma level of miR-222-3p correlated with its expression in healthy tissue; however, the concentrations of these miRNAs did not differ in plasma of breast cancer patients and healthy controls. To test whether our circulating miRNAs can be used to differentiate breast cancer patients from healthy individuals, we performed a ROC analysis. The largest area under the ROC-curve (AUC) was obtained for miR-145-5p (0.854), slightly less for miR-191-5p (0.818), and miR-21-5p was significantly inferior in this indicator (0.649). Using three microRNAs together, it was possible to separate patients from healthy women with 85 % accuracy, high specificity (94 %) and medium sensitivity (74 %). When assessing the potential of the studied miRNAs as markers of tumorigenesis in breast tissue, we found that using miR-191-5p or miR-210-3p, it is possible to distinguish cancer from healthy tissue with equally high accuracy (84% each). Although individually miR-145-5p showed medium separation accuracy (71 %), it complemented two other miRNAs in both paired and triple models. Thus, miR-145-5p and miR-191-5p can be considered potential plasma biomarkers, while miR-191-5p, miR-210-3p, and miR-145-5p can be considered potential tissue biomarkers for the diagnosis of breast cancer. The findings need to be confirmed on a more representative cohort of samples.