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Pharmacogenetics of the Primary and Metastatic Osteosarcoma: Gene Expression Profile Associated with Outcome

Alini Trujillo-Paolillo1,2, Francine Tesser-Gamba1, Maria Teresa Seixas Alves3

  • 1Genetics Laboratory, Pediatric Oncology Institute (IOP/GRAACC), Federal University of Sao Paulo, Rua Botucatu, Vila Clementino, Sao Paulo 04023-062, SP, Brazil.

International Journal of Molecular Sciences
|March 29, 2023
PubMed

Insights

This study analyzed pharmacogenetic gene expression in osteosarcoma (OS) patients. Key gene expression patterns were linked to treatment outcomes and metastasis, offering potential new prognostic factors and therapeutic targets for this common childhood bone cancer.

Area of Science:

  • Oncology
  • Pharmacogenetics
  • Molecular Biology

Background:

  • Osteosarcoma (OS) is the most prevalent bone malignancy in children and adolescents.
  • Current OS treatments face challenges with drug resistance, necessitating novel therapeutic strategies.
  • Understanding pharmacogenetic factors is crucial for improving OS patient outcomes.

Purpose of the Study:

  • To investigate the expression profiles of 32 pharmacogenetic genes in osteosarcoma.
  • To identify associations between gene expression, treatment response, and disease progression in OS.
  • To explore potential prognostic biomarkers and therapeutic targets for osteosarcoma.

Main Methods:

  • Real-time PCR was employed to analyze gene expression in 80 paired tumor specimens (pre- and post-chemotherapy, metastasis) from 33 OS patients.
  • Normal bone tissue was used as a control.
  • Statistical analysis identified correlations between gene expression and clinical outcomes.

Main Results:

  • Significant associations were found between OS outcome and the expression of 21 genes, including TOP2A, DHFR, MTHFR, BCL2L1, CASP3, FASLG, GSTM3, SOD1, ABCC1-6, ABCC10, ABCC11, ABCG2, RALBP1, SLC19A1, SLC22A1, ERCC1, and MSH2.
  • Expression of ABCC10, GGH, GSTM3, and SLC22A1 correlated with disease events.
  • Metastatic OS tissues exhibited high expression of ABCC1, ABCC3, and ABCC4, and low expression of SLC22A1 and ABCC10, suggesting a role in metastasis and resistance.

Conclusions:

  • The study identified specific pharmacogenetic gene expression patterns associated with osteosarcoma prognosis and drug resistance.
  • Aberrant expression of genes like ABCC1, ABCC3, ABCC4, SLC22A1, and ABCC10 in metastasis may drive therapeutic resistance.
  • These findings provide a basis for developing novel prognostic markers and therapeutic targets for osteosarcoma management.
Keywords:
gene expressionmetastatic osteosarcomaosteosarcomapharmacogeneticsprognostic markerstreatment response

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