Functional RNA-Seq Profiling of the Tumor Suppressor Gene OPCML in Ovarian Cancers: The Multifunctional, Pleiotropic Impacts of Having Three Ig Domains

The IgLON Family of Tumor Suppressor Genes (TSG) impact a variety of cellular processes involved in cancer and non-cancer biology. OPCML is a member of this family and as a potent TSG it is commonly silenced in many human cancers and thus an important control point in oncogenesis and tumor growth. Here, we analyze RNA-Seq expression ratios in ovarian cancers from The Cancer Genome Atlas (TCGA) to identify gene sets that exhibit a synergistic survival difference in patients in association with loss of OPCML expression. Using enrichment analyses, we reconstruct functional associations revealing broad secondary cross-talk impacts of OPCML. These results emphasize the role of OPCML's regulation of Receptor Tyrosine Kinase (RTK) signaling pathways (PI3K/AKT and MEK/ERK) while identifying three new potential RTK transcriptomic linkages to KIT, TEK and ROS1 in ovarian cancers. In addition, we show that many other known extracellular signaling receptor ligands are also transcriptionally linked to OPCML. Considering the range of cell surface and signaling pathway impacts of OPCML evident here, we expand the understanding of OPCML's broad cellular influences and conclude that OPCML is a multi-functional, pleiotropic, Tumor Suppressor.