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Updated: May 29, 2025

Serum and Plasma Copy Number Detection Using Real-time PCR
Published on: December 15, 2017
Influence of DNA Copy Number Aberrations in ABC Transporter Family Genes on the Survival of Patients with Primary
Matvey Mikhailovich Tsyganov1,2, Marina Konstantinovna Ibragimova1,2,3, Evgeny Olegovich Rodionov1
1Cancer Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences; 5, Kooperativny Street, Tomsk, Russian Federation.
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.
Insights
Chromosomal aberrations and gene expression of ABC transporters impact survival in non-small cell lung cancer (NSCLC). Specific gene alterations, like ABCB1 deletion, correlate with significantly improved metastatic-free survival (MFS).
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- Previous studies linked ABC transporters gene expression to therapy efficacy.
- Mechanisms beyond gene expression, such as chromosomal aberrations, are less explored in non-small cell lung cancer (NSCLC).
Purpose of the Study:
- To investigate chromosomal aberrations in all 49 ABC transporters genes in NSCLC.
- To assess the expression levels of selected ABC genes.
- To determine the correlation between these genetic alterations and patient survival.
Main Methods:
- Microarray analysis of DNA and RNA from 104 NSCLC patient samples.
- Assessment of gene expression and chromosomal aberrations (deletions, amplifications) of ABC genes.
- Correlation analysis with metastatic-free survival (MFS) after surgery and chemotherapy.
Main Results:
- Hypoexpression of ABCC1, ABCC2, and ABCG1 was linked to significantly higher MFS (p=0.01).
- ABCB1 deletion correlated with 100% MFS (p=0.001), while ABCG1 amplification showed survival rates below 45% (p<0.0001).
- ABCA11 deletion was associated with low MFS (38%), contrasting with ABCB9 amplification (55% survival). ABCC3 and ABCC10 amplification also showed reduced survival.
Conclusions:
- Both gene expression and chromosomal aberrations of ABC transporters are associated with patient survival in NSCLC.
- These genetic alterations may serve as potential biomarkers for predicting metastatic-free survival.
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