Prognostic utility of YBX1-mediated genes in clear cell renal cell carcinoma outcomes.

e16510 Background: The Y-box-binding protein1 (YBX1) transcription factor has been linked to a variety of biological processes such as mRNA stabilization and localization and cell-cycle progression. YBX1 has been shown to have pro-oncogenic effects in some cancers, possibly also modulating cisplatin’s effects in others. However, comparatively less regarding YBX1 has been explored in kidney renal clear cell carcinoma (ccRCC), the most common kind of kidney cancer. This in silico study explores the relationship between YBX1 and associated regulatory targets in ccRCC cases. Methods: The MSig database was utilized to generate a list of genes which contained one or more YBX1 binding sites in their promoter region based on ChIP-seq data. Kaplan-Meier plots of overall survival in ccRCC cases based on YBX1 and YBX1-regulated gene expression were generated using TCGA data on the KMPlot platform with “high” and “low” expression cutoffs based on quartiles. Multiple hypothesis testing was corrected by adjusting the significant p-value cutoff to a FDR >0.05 (adjusted p-value cutoff is 0.023). Enrichment and network analysis was then conducted on genes shown to be differentially expressed in respect to outcome through the Cytoscape and Metascape platform to see which over-represented biological pathways may mediate outcome (p<0.01 for significance). Results: Out of 76 initial genes, 33 showed differential expression in regards to survival, including YBX1 itself. Enrichment analysis highlighted biological processes such as negative regulation of mRNA metabolic processes and Nop56p-associated rRNA complex formation as possible ways YBX1 and its related targets can affect outcomes. A variety of genes were highlighted by the network analysis, such as the membrane trafficking gene YIF1A and acetyltransferase KAT8 among others. Conclusions: Similar to what has been shown in other types of cancers, YBX1 and its regulatory constituents have been linked to ccRCC outcomes, possibly due to its role regarding mRNA regulation as highlighted by our enrichment analysis. Other interactions mediated by genes such as the cell cycle regulator CCAR2 offer other pathways through which YBX1 can mediate outcome. Previously being linked with cisplatin resistance in other cancers such as breast, YBX1 offers a suitable target for further wet-lab research regarding its role in ccRCC.