High-grade serous ovarian cancer (HGSOC) is the commonest subtype of epithelial ovarian cancer. β-TrCP (encoded by BTRC) is a component of ubiquitin-proteasome system, a posttranslational process for protein regulation and homeostasis. The role of BTRC levels in HGSOC is not fully explored. The aim of this study was to investigate, using bioinformatics approach, the impact of BTRC levels on HGSOC. Publicly available transcriptomic data from HGSOC patients (TCGA) were used. First, the overall survival of patients in the lower quartile of BTRC expression was compared to those in the upper quartile. Next, differential gene expression analysis (DEA) was performed on the RNA-seq data to find genes that differ significantly in the two groups. Finally, gene set enrichment analysis (GSEA) using KEGG and GO databases were done to identify signaling pathways and mechanisms significantly upregulated in either of the two groups.

Our findings showed that HGSOC patients with high BTRC levels had significantly worse overall survival compared to those with low levels (log-rank = 0.0035). DEA of RNA-seq data returned a total of 371 significantly differentially expressed genes among the two groups. GSEA elucidated that high-BTRC expression patients were characterized by significant upregulation of many pathways and processes pertaining to cellular growth, proliferation, survival, stemness and development. In contrast, patients with low BTRC expression have many significantly upregulated pathways and processes related to mitochondrial function, immunity, and inflammation responses. Those differentially upregulated pathways and processes likely contribute to the variable survival outcomes of HGSOC patients. These findings suggest that BTRC expression levels, pending experimental validation, might be a candidate biomarker for informing combinatorial chemotherapy strategies that target implicated signaling pathways in HGSOC.

Keywords: HGSOC, RNAseq, Gene set enrichment analysis, BTRC, β-TrCP