Abstract 2253: 5 Gene prognostic signature for dedifferentiated liposarcomas

Abstract

Abstract Introduction: Liposarcomas, despite being rare consist of a number of entities spanning low to high grade sarcomas. De-differentiated liposarcoma (DDLS) is associated with increased frequency of recurrence and lower overall survival. We aimed to identify gene expression changes associated with OS in DDLS. Secondary aims was to postulate a mechanism for DDLS. Methods: We analysed data from gene expression omnibus (GEO, ID = GSE30929) to identify genes associated with DDLS (n=39). A signature representing genes overexpressed in DDLS was then applied to an independent dataset, utilising data from The Cancer Genome Atlas (TCGA, n=58 DDLS) to segregate samples based on gene expression and groupings compared for survival. Results: A 5 gene signature was generated consisting of genes with increased expression in DDLS and its relation to OS. The signature was significantly enriched for genes involved in lipid metabolism (AQP7, PRKAR2B, FABP4 p<0.01) and genes involved in the cell cycle and cell proliferation (FBN2, CEBPA p<0.01). Segregation of DDLS in the TCGA cohort on the basis of median gene signature score gave a significant difference in overall survival. High score (stronger DDLS signature) was associated with a lower median survival(33.5 vs 76.4 months, p = 0.027), and poorer 2 year (63.4% vs 89.2%) and 5 year survival (20.6% vs 71.1%). The survival difference remained significant when applied to retroperitoneal DDLS only (n=51, median survival 34.5 vs 54.2 months, p = 0.034) and poorer 2 year survival (. A postulated mechanism is that DDLS have gained deficiency in AQP7, PRKAR2B and FABP4 leading to fatty acid and glycerol accumulation in cells, increasing cancer cell replication. CEBPA inhibits CDK4 and a deficiency of CEBPA in DDLS leads to up regulation of CDK4, increasing cell proliferation. An upregulation of FBN2 in DDLS up regulates TGF-β1, increasing cell proliferation. Conclusion: Gene expression changes associated with dedifferentiated liposarcomas include changes in cell cycle checkpoint regulation. The signature is associated with poorer overall survival in DDLS and can be used to prognosticate patients. Citation Format: Deanna Ng, Nicholas Shannon, Johnny Ong, Melissa Teo. 5 Gene prognostic signature for dedifferentiated liposarcomas [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2253. doi:10.1158/1538-7445.AM2017-2253