Characterization of alternative mRNA splicing associated with tumor thrombus in clear-cell renal cell carcinoma

Approximately 10% of Renal Cell Carcinoma (RCC) tumors form a thrombus that invades into nearby vasculature and is associated with lower survivability. However, the mechanisms driving tumor thrombus formation and progression are poorly understood. We therefore examined a publicly available RNAseq dataset of samples from RCC patients containing tumors with and without thrombi, as well as associated normal kidney tissues, and compared them. Using cell deconvolution, we found indications that kidney tumors and thrombi are associated with loss of mature kidney-specific cell types and gain of proliferative characteristics. Moreover, we identified a set of transcripts that are alternatively spliced between tumors with and without thrombi. Using motif enrichment analysis for known RNA binding proteins we found putative splicing regulators that are presumably associated with thrombus formation. We believe that this study will assist in unraveling cellular and molecular mechanisms of tumor progression and thrombus formation in RCC.