Abstract
Increasingly, many researchers are focusing on the sensitivity in breast tumors (BC) to certain chemotherapy drugs and have personalized their research based on the assessment of this sensitivity. One such personalized approach is to assess the chemotherapy’s gene expression, as well as aberrations in the number of DNA copies—deletions and amplifications with the ability to have a significant effect on the gene’s activity. Thus, the aim of this work was to study the predictive and prognostic significance of the expression and chromosomal aberrations of eight chemosensitivity genes in breast cancer patients. Material and methods. The study involved 97 patients with luminal B breast cancer IIB–IIIB stages. DNA and RNA were isolated from samples of tumor tissue before and after treatment. Microarray analysis was performed for all samples on high-density microarrays (DNA chips) of Affymetrix (USA) CytoScanTM HD Array and Clariom™ S Assay, human. Detection of expression level of seven chemosensitivity genes—RRM1, ERCC1, TOP1, TOP2a, TUBB3, TYMS, and GSTP1—was performed using PCR real-time (RT-qPCR). Results. The expression of the RRM1 (AC scheme), TOP2α, TYMS, and TUBB3 genes in patients with an objective response to treatment (complete and partial regression) is higher than in patients with stabilization and progression (p < 0.05). According to our results, the presence of a high level of GSTP1 in a tumor biopsy is associated with the low efficiency of the NAC CP scheme (p = 0.05). The presence of RRM1 deletion is associated with complete and partial regression, as for the TOP1 and TUBB3 genes (p < 0.05). Higher rates of metastatic survival are associated with a high level of expression and amplification of the GSTP1 gene (log-rank test p = 0.02 and p = 0.05). Conclusion. Thus, a complex assessment of the chemotherapy’s gene expression is important not only for understanding the heterogeneity and molecular biology of breast cancer but also to obtain a more accurate disease prognosis.
Highlights
This article is an open access articleThe most important aspect of personalized treatment of cancer patients is the resistance and sensitivity to specific chemotherapeutic drugs [1]
It has been established that the expression and/or co-expression of genes for chemosensitivity in tumor tissues is closely related to chemoresistance and prognosis in patients with breast cancer [2]
Gene expression, it showed a high relationship with the effectiveness of treatment, is a variable value
Summary
The most important aspect of personalized treatment of cancer patients is the resistance and sensitivity to specific chemotherapeutic drugs [1]. For this purpose, it is possible to determine markers of chemosensitivity in tumor tissue. Many studies have shown that the expression and/or co-expression of several genes, such as ERCC1, RRM1, TOP1, TOP2α, TUBB3, TYMS, and GSTP1, in tumor tissues is closely related to chemoresistance distributed under the terms and conditions of the Creative Commons. Clinical studies have shown that high ERCC1 expression is associated with resistance to platinumbased chemotherapy [3], as well as overexpression of glutathione-S-transferase P1 (GSTP1), which belongs to the family of metabolic enzymes, which is involved in the detoxification of some anticancer drugs by conjugating with glutathione [4], which is associated with low efficacy of chemotherapy based on anthracyclines and taxanes, as well as low rates of disease-free and overall survival [4,5].
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