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.

PubMed
Abstract

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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