Expression of drug resistance-related genes in head and neck squamous cell carcinomas and normal mucosa

S Hirata1, O Katoh, T Oguri

  • 1Department of Otorhinolaryngology, Hiroshima University Faculty of Medicine. hirata@mcai.med.hiroshima-u.ac.jp

Insights

This study found higher Topoisomerase IIalpha gene expression in head and neck squamous cell carcinoma (HNSCC), particularly in metastatic tumors. This suggests topoisomerase-targeting drugs may be effective for HNSCC treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Head and neck squamous cell carcinoma (HNSCC) is a significant health concern.
  • Understanding the molecular mechanisms of drug resistance in HNSCC is crucial for effective treatment.
  • Several genes, including multidrug resistance (MDR) genes and topoisomerases, are implicated in cancer drug resistance.

Purpose of the Study:

  • To investigate the expression levels of key drug resistance genes in HNSCC.
  • To correlate gene expression with biological characteristics and in vivo drug resistance in HNSCC.
  • To evaluate the potential of targeting specific genes in HNSCC therapy.

Main Methods:

  • Quantitative reverse transcription-polymerase chain reaction (RT-PCR) was used to analyze gene expression.
  • Fifty-eight human samples (45 HNSCC, 13 normal mucosa) were analyzed.
  • Expression levels of MDR1, MRP, cMOAT, LRP, Topo IIalpha, Topo IIbeta, and Topo I genes were quantified.

Main Results:

  • MDR1, MRP, LRP, Topo IIalpha, Topo IIbeta, and Topo I mRNA were detected in all samples; cMOAT mRNA was not detected.
  • Topo IIalpha gene expression was significantly higher in HNSCC compared to normal head and neck mucosa (P=0.0298).
  • Topo IIalpha mRNA levels were also significantly elevated in metastatic lymph node samples of HNSCC (P=0.0205).
  • No significant differences in gene expression were observed between platinum drug-exposed and non-exposed samples.

Conclusions:

  • Elevated Topo IIalpha expression in HNSCC, especially in metastatic tumors, suggests its potential as a therapeutic target.
  • Topoisomerase-targeting drugs may be effective for treating HNSCC, particularly advanced cases.
  • The expression of the studied genes in HNSCC does not appear to be associated with prior platinum drug exposure.