miRNA EXPRESSION PROFILE ASSOCIATED WITH AGGRESSIVENESS OF BREAST CANCER OF DIFFERENT MOLECULAR SUBTYPES

Borikun T.V.¹, Bazas V.M.², Zadvornyi T.V.¹, Lukianova N.Yu.¹

• ¹R.E. Kavetsky Institute of experimental pathology, oncology and radiobiology of NAS of Ukraine
• ²Kyiv City Clinical Oncology Center, Kyiv, Ukraine

Aim: to identify the expression profile of tumor-associated microRNAs and assess their clinical significance for predicting the breast cancer (BC) course of a particular molecular subtype. Object and methods: the study was conducted on clinical material of 151 patients with stage I–II BC aged 55.2 ± 4.1 years, who were hospitalized in the Kyiv City Clinical Oncology Center during 2013–2016. MicroRNA levels were determined using real-time reverse transcriptional polymerase chain reaction. Studies of the expression of steroid hormone receptors, HER2/neu and the proliferation marker Ki-67 in breast cancer cells were performed on paraffin sections of the operative material using the immunohistochemical method. Statistical processing of the obtained results was performed using the program GraphPad Prism, v.6.05 (GraphPad Software, Inc., San Diego, USA) taking into account the nature of the distribution of the obtained data. Results: It was found that high levels of expression of miRNA-10b, -126 and -221 and low miRNA-34a, -181a, -200b, -205 and -320a are characteristic of luminal A subtype of breast cancer; luminal B — high levels of miRNA-34a, -155, -200b, -205 and -320a and low levels of miRNA-10b, -126 and -221; HER2/neu-positive — high levels of miRNA-126 and -221 and low — mRNA-10b, -34a, -200b, -205 and -320a; basal — high levels of expression of miRNA-10b, -21 and -34a. The presence of correlations between the level of expression of tumor-associated microRNAs with the main clinical and pathological characteristics of patients with breast cancer of different molecular subtypes was determined. The relationship between the expression levels of the studied microRNAs and the rates of 3-year recurrence-free and 5-year overall survival in patients with breast cancer of different molecular subtypes was demonstrated. Conclusion: the possibility of using expression indicators of tumor-associated miRNAs to predict the aggressiveness of different molecular subtypes of breast cancer and assess the risk of recurrence is substantiated.