Abstract 5400: Pharmacogenomics in the primary and metastatic osteosarcoma: Gene expression profile associated with outcome

Purpose: Osteosarcoma (OS) is the most common malignant bone tumor in children and adolescents. Drug resistance and unfavorable outcome are problems that still affect an important percentage of OS patients. Thus, the aim of the present study was to analyze the expression of genes related to pharmacogenomics in OS. Procedure: The expression of 32 target genes in 80 paired specimens (pre-chemotherapy primary tumors, post-chemotherapy primary tumors and pulmonary metastases), from 33 patients diagnosed with OS, were analyzed by the real-time PCR methodology. Five normal bone specimens were used as calibrators (control). The target genes are related to drug transport, drug detoxification, doxorubicin and folate pathway, DNA repair, cell cycle and apoptosis. Results: The higher ABCC3 gene expression in pre-chemotherapy primary tumors was associated with worse event-free survival (EFS) (p=0.048, HR=3.41). The higher TOP2A gene expression in post-chemotherapy primary tumors was associated with worse overall survival (OAS) and EFS (p=0.015, HR=5,37; p=0.006, HR=6.36; respectively). The lower MTHFR gene expression in pulmonary metastases was associated with worse OAS and EFS (p=0.027, HR=3.27; p=0.024, HR=3.1; respectively), as well as the lower BCL2L1 gene expression (p=0.018, HR=3.53; p=0.019, HR=3.29). Furthermore, lower expression of the RALBP1, ABCC2 and SOD1 genes in the pulmonary metastasis specimens were associated with worse EFS (p=0.022, HR=3.26; p=0.048, HR=3.16; p=0.027, HR=3.14; respectively). Moreover, the pulmonary metastases presented higher expression of the ABCC1 and ABCC4 genes (p=0.049; p =0.039; respectively) and lower expression of the ABCC10, ERCC2, MSH2, SLC22A1, SOD1 and TOP2A genes (p=0.049; p=0.043; p=0.043; p=0.017; p=0.048; p=0.005; respectively) than pre-chemotherapy primary tumors. Conclusion: Therefore, the pharmacogenomics profile may be useful as prognostic factors as well as therapeutic targets. Thus, our findings may, in the future, contribute to clinical management in the primary and metastatic OS. Citation Format: Alini Trujillo-Paolillo, Francine Tesser-Gamba, Antonio Sergio Petrilli, Maria Teresa Alves, Reynaldo Jesus Garcia-Filho, Renato Oliveira, Silvia Regina Toledo. Pharmacogenomics in the primary and metastatic osteosarcoma: Gene expression profile associated with outcome [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5400.