Expression Profiles of Osteosarcoma That Can Predict Response to Chemotherapy

Abstract

Osteosarcoma is the most common malignant bone tumor in children. After initial diagnosis is made with a biopsy, treatment consists of preoperative chemotherapy followed by definitive surgery and postoperative chemotherapy. The degree of tumor necrosis in response to preoperative chemotherapy is a reliable prognostic factor and is used to guide the choice of postoperative chemotherapy. Patients with tumors, which reveal z90% necrosis (good responders), have a much better prognosis than those with <90% necrosis (poor responders). Despite previous attempts to improve the outcome of poor responders by modifying the postoperative chemotherapy, their prognosis remains poor. Therefore, there is a need to predict at the time of diagnosis patients' response to preoperative chemotherapy. This will provide the basis for developing potentially effective therapy that can be given at the outset for those who are likely to have a poor response. Here, we report the analysis of 34 pediatric osteosarcoma samples by expression profiling. Using parametric two-sample t test, we identified 45 genes that discriminate between good and poor responders (P < 0.005) in 20 definitive surgery samples. A support vector machine classifier was built using these predictor genes and was tested for its ability to classify initial biopsy samples. Five of six initial biopsy samples that had corresponding definitive surgery samples in the training set were classified correctly (83%; confidence interval, 36%, 100%). When this classifier was used to predict eight independent initial biopsy samples, there was 100% accuracy (confidence interval, 63%, 100%). Many of the predictor genes are implicated in bone development, drug resistance, and tumorigenesis. (Cancer Res 2005; 65(18): 8142-50)

Anti‐apoptotic role of TWIST and its association with Akt pathway in mediating taxol resistance in nasopharyngeal carcinoma cells

“…12,13 In osteosarcoma, upregulation of TWIST is found to be a predictor in patients with poor response to chemotherapy. 17 Several in vitro studies also agree with these findings. For example, exogenous TWIST expression in mouse embryonic fibroblasts promotes soft agar colony formation, 7 indicating its role in malignant transformation.…”

Osteosarcoma

“…Simple classifications that were possible for the translocation-associated sarcomas were not possible for osteosarcoma, and these analyses thus far have produced few tangible results. (66,67) Perhaps suggesting whole-genome sequencing may be of value in osteosarcoma is the ability of this approach to identify consistently mutated pathways in genetically complex malignancies such as lung adenocarcinoma. (68) Whether a consistent pattern will emerge from whole-genome sequencing analyses of osteosarcoma awaits completion of these studies.…”

Molecular characterization of the response to chemotherapy in conventional osteosarcomas: Predictive value of HSD17B10 and IFITM2

“…Only few studies comparing gene expression profiles of pretherapeutic biopsies of responsive or nonresponsive patients with an osteosarcoma are available in the literature. [11][12][13] This may be because of the rarity of the tumor and to the difficulty to get frozen specimens from preoperative material. Previous studies have shown that in chemoresistant tumors, genes involved in osteoclastogenesis, extracellular matrix remodeling, bone development, tumor progression, drug resistance and angiogenesis are up-regulated.…”

“…Previous studies have shown that in chemoresistant tumors, genes involved in osteoclastogenesis, extracellular matrix remodeling, bone development, tumor progression, drug resistance and angiogenesis are up-regulated. [11][12][13][14][15][16] It is intriguing that there is apparently no overlap between the gene sets identified by the different groups of investigators.…”