Congresso Internacional do GRAACC

Dados do Trabalho


IGFBP5 in osteosarcoma tumorigenesis: gene expression profile among metastatic and non-metastatic patients


Osteosarcoma (OS) is the most frequent primary malignant bone tumor among children and adolescents, with a peak of incidence in the second decade of life. The presence of metastasis at diagnosis significantly decreases the chances of survival of OS patients and new therapy approaches are needed. The IGFBP5 gene is related to osteoblasts metabolism and some studies have pointed a role of its low expressions in OS development and metastasis. In this study, we aimed to establish an IGFBP5 gene expression profile in metastatic and non-metastatic OS patients among treatment and development of the disease. Fresh-frozen tumor samples were obtained from 40 patients admitted to treatment at the Pediatric Oncology Institute (IOP/GRAACC/UNIFESP) and divided by clinical status: metastatic or non-metastatic disease. For each patient, samples before and after chemotherapy treatment were obtained, as well as metastasis and lung tissue surrounding metastasis samples of the metastatic patients. A quantitative real-time PCR was used to investigate IGFBP5 expression. Our analyses demonstrate that non-metastatic patients presented lower IGFBP5 expression in their pre-chemotherapy samples compared with metastatic patients, suggesting that low expressions of this gene could help triggering the OS tumorigenesis but that its action alone is not sufficient to activate the metastatic process. Heterogeneity in IGFBP5 expression within groups was also seen. Additionally, we observed that IGFBP5 and two MAPK genes, a downstream pathway in the IGFBP5 axis, are differentially expressed in OS samples of non-metastatic patients. Further investigation about these genes modulations might lead to a better understanding of OS development and metastasis.


Genética/ Terapia de precisão


Giovanna Manga Guimarães, Francine Tesser-Gamba, Antônio Sérgio Petrilli, Maria Teresa Seixas Alves, Reynaldo Jesus Garcia-Filho, Renato Oliveira, Silvia Regina Caminada Toledo