Abstract
Metastasis is a major factor associated with poor prognosis in cancer, but little is known of its molecular mechanisms. Although the clinical behavior of soft tissue sarcomas is highly variable, few reliable determinants of outcome have been identified. New markers that predict clinical outcome, in particular the ability of primary tumors to develop metastatic tumors, are urgently needed. Here, we have chosen leiomyosarcoma as a model for examining the relationship between gene expression profile and the development of metastasis in soft tissue sarcomas. Using cDNA microarray, we have identified a gene expression signature associated with metastasis in sarcoma that allowed prediction of the future development of metastases of primary tumors (Kaplan-Meier analysis P = 0.001). Our finding may aid the tailoring of therapy for individual sarcoma patients, where the aggressiveness of treatment is affected by the predicted outcome of disease.
Highlights
Soft tissue tumors are a heterogeneous group of mesenchymal tumors that arise as soft tissue masses and that frequently exhibit the differentiated features of adult soft tissue [1]
Cy5-labeled sarcoma cDNA was cohybridized with Cy3-labeled reference cDNA from pooled human cell lines [4] that served as an internal standard for the comparison of different experiments
As we were interested in the expression differences that may characterize metastatic sarcomas, we compared the gene expression profiles of the 20 primary tumors (P) and 7 metastatic tumors (M) with supervised class comparison analysis with tumors in group 2 developed metastases
Summary
Soft tissue tumors are a heterogeneous group of mesenchymal tumors that arise as soft tissue masses and that frequently exhibit the differentiated features of adult soft tissue [1]. The disease accounts for ϳ1% of all cancers and is associated with a substantial mortality rate of ϳ50%, which is related in part to its propensity for metastasis [1, 2]. The clinical behavior of soft tissue sarcomas is highly variable, but few reliable determinants of outcome have been identified [2, 3]. New markers that predict clinical outcome, in particular the propensity of primary tumors to develop metastatic tumors, are urgently needed and would be of great clinical use, allowing for more selective treatment strategies. We have chosen leiomyosarcoma as a model to assess the relationship between gene expression profiles determined on cDNA microarray and the clinical outcome of metastasis in soft tissue sarcomas
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