Interrelations of sphingolipid and lysophosphatidate signaling with immune system in ovarian cancer

Publication date: Available online 10 April 2019Source: Computational and Structural Biotechnology JournalAuthor(s): Anastasia Meshcheryakova, Martin Svoboda, Markus Jaritz, Felicitas Mungenast, Martina Salzmann, Dietmar Pils, Dan Cacsire Castillo-Tong, Gudrun Hager, Andrea Wolf, Elena Ioana Braicu, Jalid Sehouli, Sandrina Lambrechts, Ignace Vergote, Sven Mahner, Peter Birner, Philip Zimmermann, David N. Brindley, Georg Heinze, Robert Zeillinger, Diana MechtcheriakovaAbstractThe sphingolipid and lysophosphatidate regulatory networks impact diverse mechanisms attributed to cancer cells and the tumor immune microenvironment. Deciphering the complexity demands implementation of a holistic approach combined with higher-resolution techniques. We implemented a multi-modular integrative approach consolidating the latest accomplishments in gene expression profiling, prognostic/predictive modeling, next generation digital pathology, and systems biology for epithelial ovarian cancer. We assessed patient-specific transcriptional profiles using the sphingolipid/lysophosphatidate/immune-associated signature. This revealed novel sphingolipid/lysophosphatidate-immune gene-gene associations and distinguished tumor subtypes with immune high/low context. These were characterized by robust differences in sphingolipid−/lysophosphatidate-related checkpoints and the drug response. The analysis also nominates novel survival models for stratification of patients with CD68, LPAR3, SMPD1, PPAP2B, an...
Source: Computational and Structural Biotechnology Journal - Category: Biotechnology Source Type: research