DNA Repair Genes Overexpressed in Non-Small Cell Lung Cancer

Scientists in Turin, Italy, investigated the expression of genes involved in DNA repair and replication as predictive markers of response to chemotherapy in non-small cell lung cancer (NSCLC). The study evaluated differential mRNA levels of 22 DNA repair genes and 6 genes involved in DNA replication in tumors compared to corresponding normal lung tissues of 50 consecutive chemo-naive resected NSCLC patients. The research team found that 20 of 30 (67%) genes were significantly overexpressed, mostly belonging to double-strand break (DSBR) pathways, while others were significantly underexpressed.

Key Takeaways:

  • 20 out of 30 (67%) genes involved in DNA repair and replication pathways were significantly overexpressed in NSCLC tumors, mostly belonging to DSBR pathways.
  • 7 out of 30 (23%) genes showed no significant difference in transcript levels between paired tumor and normal samples.
  • The transcriptional overexpression of 4 genes (XRCC5, TOP3B, TYMS, and UNG) showed significant correlation with a shorter patients' outcome at the univariate analysis.
  • The stage of disease appeared as an independent factor affecting prognosis, whereas overexpression of DSBR and REP genes was associated with a more aggressive phenotype.
  • Poorly differentiated carcinomas showed significantly higher transcript overexpression of DSBR and REP genes compared to well-differentiated carcinomas.
  • The study's findings suggest that genes involved in DNA repair and replication pathways may serve as predictive markers of response to chemotherapy in NSCLC.

Statistics:

  • 67% of genes involved in DNA repair and replication pathways were significantly overexpressed in NSCLC tumors.
  • 23% of genes showed no significant difference in transcript levels between paired tumor and normal samples.
  • 4 out of 30 (13.3%) genes showed significant correlation with a shorter patients' outcome at the univariate analysis.
  • The study involved 50 consecutive chemo-naive resected NSCLC patients.

Sources:

  • Saviozzi, S., et al. "Non-Small Cell Lung Cancer Exhibits Transcript Overexpression of Genes Associated with Homologous Recombination and DNA Replication Pathways." Cancer Research, vol. 69, no. 8, 2009, pp. 3390-3396.
  • American Association Cancer Research, "Cancer Research," 615 Chestnut St., 17TH Floor, Philadelphia, PA 19106-4404, USA.