Dados do Trabalho

Título

Pharmacogenomics of the primary and metastatic osteosarcoma: gene expression profile associated with outcome

Resumo

Osteosarcoma (OS) is the most common malignant bone tumor in children and adolescents. In recent decades, OS treatment has reached a plateau and drug resistance is still a major challenge. Therefore, the aim of the present study was to analyze the expression of genes related to pharmacogenomics in OS. The expression of 32 target genes in 80 paired specimens (pre-chemotherapeutic primary tumor, post-chemotherapeutic primary tumor and pulmonary metastasis), from 33 patients diagnosed with OS, were analyzed by the real-time PCR methodology. As the calibrators (control), 5 normal bone specimens were used. The present study identified associations between OS outcome and expression of the genes TOP2A, DHFR, GGH, MTHFR, BCL2L1, CASP3, FASLG, GSTM3, GSTT1, SOD1, ABCB1, ABCC1, ABCC2, ABCC3, ABCC4, ABCC5, ABCC6, ABCC10, RALBP1, SLC19A1, SLC22A1, ERCC1, ERCC2 and MSH2. In addition, gene expression of ABCC10, GGH, GSTM3 and SLC22A1 was associated with the disease event, and the metastasis specimens showed high expression profile of ABCC1, ABCC3, ABCC4 and ABCC6 and low expression of SLC22A1, which is possibly an important factor for resistance in OS metastasis. Therefore, our findings may, in the future, contribute to clinical management, both as prognostic factors and as possible therapeutic targets.