Influence of DNA Copy Number Aberrations in ABC Transporter Family Genes on the Survival of Patients with Primary Operatable Non-Small Cell Lung Cancer.

Abstract

Purpose: Previous research has shown, that ABC transporters gene expression level can predict the efficacy of therapy. However, other mechanisms of gene activity are rarely considered, especially in non-small cell lung cancer (NSCLC). Thus, the purpose of the work was to assess chromosomal aberrations of all 49 ABC transporters genes and the expression levels of some ABC genes, as well as their correlation with survival.

Materials and methods: The surgical material of 104 patients with NSCLC was used in this study. Treatment included surgery and 3 courses of adjuvant chemotherapy with "platinum doublets". DNA and RNA were isolated from the samples, followed by microarray analysis to assess the expression and chromosomal aberrations (deletions and amplifications) of ABC genes.

Results: Metastatic-free survival (MFS) was higher with ABCC1, ABCC2, and ABCG1 hypoexpression at a statistically significant level (p=0.01). The presence of deletion in ABCB1 correlates with 100% MFS (p=0.001). The survival rates with ABCG1 amplification are not higher than 45% (p<0.0001). ABCA11 deletion is associated with a low MFS rate (38%) versus 91% with normal copy number (p=0.006). ABCB9 analysis showed opposite results, with survival rates of 55% and 91% in the presence of amplification and normal copy number, respectively (p=0.006). ABCC subfamily genes showed a similar result in the presence of amplification, where ABCC3 and ABCC10 account for 64% and 60% survival, respectively (p=0.005, p=0.01).

Conclusion: Thus, not only expression but also chromosomal aberrations were found to be associated with patient survival. These findings could be a potential marker of metastatic-free survival.