Research on breast cancer

On 12 October, in a public session of the RSU Doctoral Committee of Medicine, Rīga Stradiņš University, that will be held in the Hippocrates Lecture Theatre, Riga, 16 Dzirciema iela., Ms Dagnija Kalniete will defend a doctoral thesis MicroRNA Expression as a Prognostic Indicator for Breast Cancer Development.

Breast cancer is one of the most common malignancies and the most frequent cause of death among women worldwide. Breast cancer is a clinically, morphologically and genetically heterogeneous disease and the pace of the disease, response to therapy, side effects and outcome depend on the heterogeneous nature of the disease.

There are several types of breast cancer, and this classification algorithm is used in clinical practice to evaluate possible development of the disease and select the most appropriate treatment strategy. However, this algorithm does not provide enough information to predict the development of the disease, therefore, there is a need for a new prognostic marker in clinical practice. Such potential biomarkers could be microRNAs- in a length of approximately 18–25 nucleotides noncoding molecules that regulate gene expression at the post transcriptional level. These molecules are involved in such critical cell events as differentiation, growth and apoptosis hence these molecules play an important role in the pathogenesis of the cancer. Expression of the different microRNAs in cancer tissues is altered and this changed expression correlates with clinical and pathophysiological features of cancer. MicroRNAs can act similarly as oncogenes or tumour suppressor genes and expression is either up-regulated or down-regulated.

Triple-negative (TN) breast cancer is among the most aggressive types of cancer TN breast cancers are referred to as estrogen receptor (ER) negative, progesterone receptor (PR) negative, and human epidermal growth factor receptor (HER2) negative tumours. TN breast cancer patients harbouring the BRCA1 mutations at the time of the diagnosis are younger, have smaller tumour size, and have significantly better recurrence-free and disease-specific survival rates than TN breast cancer patients with no mutations in the BRCA1 gene.

The aim of this study was to look for the miRNA that differs in expression between TN hereditary and sporadic tumours and associate expression level of some miRNA to overall survival of TN breast cancer patients. To explain different expression in TN-H and TN-S breast cancer tissues, analysis of gene expression profile was carried out.

Relative expression of four MicroRNAs (miR-21, miR-29a, miR-31, and miR-214) is significantly higher in breast cancer tissues than in normal breast epithelial tissues, though solely miR-214 reached the level of statistical reliability. Besides, TN breast cancer patients with high expression level of miR-214 have significantly worse overall survival than patients with low expression of miR-214. Twenty genes with different expressions were detected among TN-H and TN-S breast cancer group, besides three of the discovered genes – C12ORF23, C1ORF19 and AMMECR1L – regulate miR-21 and miR-214 expression.