Prognostic and Predictive Significance of mRNA Expression of ABC-transporter Genes in Patients with Non-small Cell Lung Cancer

Abstract

Introduction. To date, one of the reasons for the ineffectiveness of chemotherapy in various malignant neoplasms, including lung cancer, is the formation of the multidrug resistance (MDR) phenotype in tumor cells, which is caused by the expression of ABC transporter genes.Aim. The aim of this work was to assess the expression of ABC-transporter genes during chemotherapy and to analyze the relationship with the effectiveness of chemotherapy and prognosis of the disease.Materials and methods. We used biopsy and surgical material from 91 patients with stage IIB–IIIA non-small cell lung cancer (NSCLC). The treatment regimen included: 2 courses of neoadjuvant chemotherapy (NAC), surgery and 3 courses of adjuvant chemotherapy (ACT) with platinum doublets. RNA was isolated from the samples, followed by quantitative PCR to assess the expression of genes ABCB1, ABCC1, ABCC2, ABCC5, ABCG1, ABCG2.Results and discussion. It was shown that the level of expression of the studied genes was not associated with the effect of NAC in patients with lung cancer, except for the ABCC5 gene, which showed a relationship at the level of a pronounced trend (p = 0.07). It was also shown that in the group of patients with an objective response to chemotherapy, the frequency of decreased expression of the ABCC1 (p = 0.01) and ABCC5 (p = 0.004) genes was statistically significantly higher than in the group of patients with stabilization. Further, using the Kaplan – Meier method, it was found that a decrease in expression is associated with high rates of metastatic-free survival (MFS). The highest rates of 5-year MFS (more than 85 %) are observed in patients with a decrease in the expression of the ABCB1 and ABCG2 genes, log-rank test p = 0.0007 and p = 0.002, respectively.Conclusion. Thus, it has been shown that changes in the expression of ABC transporter genes are associated with the effectiveness of chemotherapy and the prognosis of the disease. The data obtained can be used as a basis for the detection of potential drug targets.

Keywords

• экспрессия генов
• немелкоклеточный рак легкого
• abc-транспортеры
• прогноз заболевания
• эффект химиотерапии