Gene expression analysis of ABC transporter family in breast tumors: relationship with chemotherapy effect and disease prognosis

Abstract

Background. One of the main reasons of the ineffectiveness of chemotherapy is still considered to be the formation of the multidrug resistance phenotype of the tumor due to the expression of energy-dependent proteins of ABC transporters. Our previous studies for some ABC genes have established that the expression of these genes correlates with the effectiveness of neoadjuvant chemotherapy (NAC). Some of the clinical studies indicate that ABC transporters can influence not only the formation of chemoresistance in the tumor, but also the progression, invasion and metastasis of the tumor node. Objective: to evaluate the level of transcription of all 49 known ABC genes in a breast tumor before and after treatment and their prognostic significance. Materials and methods. The study included 31 patients with a diagnosis of stage IIA – IIIB breast cancer. RNA was isolated from paired samples of tumor tissue before and after NAC. A microarray study of all tumor samples was performed on ClariomТМ S Assay, human microarrays. Using microarray studies, the expression of 49 genes of the ABC transporter family was studied. Analysis of the microchip data was carried out using the program Transcriptome Analysis Console (TAC) software 4.0. Results. It was found that changes in the expression (increase/decrease during NAC) of the ABCA5, ABCA7, ABCB1, ABCB4, ABCB11, ABCC1, ABCC10, ABCC11, ABCG1, ABCG2, ABCG4, ABCG5, ABCG8 genes are statistically significantly associated with the response to NAC. In addition, the prognostic significance of ABCB1 and ABCB4 gene expression was established. Survival analysis showed that 5-year survival rates in patients with high gene expression of ABCB1 and ABCB4 are lower compared to patients with low expression of these genes (log-rank-test p = 0.001 and 0.04 respectively). Conclusion. Data were obtained on the relationship of gene expression of the ABC transporter family with the effect of NAC in patients with breast cancer and the outcome of the disease. The prognostic potential of the ABCB1 and ABCB4 genes in patients with breast cancer has been established.

Keywords

• breast cancer
• microarray
• transcript
• abc transporters
• neoadjuvant chemotherapy
• prognosis