# Prognostic Significance of Overexpression of BCL9 and TPX2 in High-Grade Clear Cell Renal Cell Carcinoma: Prognostic Markers for Metastasis and Survival

## TL;DR

This study finds that high levels of BCL9 and TPX2 proteins in kidney cancer are linked to worse patient outcomes and could help predict survival and metastasis.

## Contribution

The study identifies BCL9 and TPX2 as novel prognostic markers for high-grade clear cell renal cell carcinoma.

## Key findings

- BCL9 and TPX2 are significantly upregulated in ccRCC compared to normal tissue.
- High BCL9 levels correlate with shorter progression-free survival, while high TPX2 levels correlate with shorter overall survival.
- BCL9 is linked to Wnt signaling, and TPX2 to cell cycle regulation in ccRCC.

## Abstract

Clear-cell renal cell carcinoma (ccRCC) is a kidney cancer associated with poor prognosis and limited treatment options. Identifying new prognostic markers is crucial. This study investigates the potential of BCL9 and TPX2, two proteins involved in cancer progression, to predict patient outcomes This study analyzed protein abundance data from the CPTAC cohort (110 ccRCC and 84 NAT samples) using LC-MS/MS. BCL9 and TPX2 were validated via immunohistochemistry (IHC) in an independent cohort (52 ccRCC samples). Patients were stratified into high- and low-expression groups based on IHC scores. Survival analyses were conducted, and Reactome pathway enrichment analysis was performed. BCL9 and TPX2 were significantly upregulated in ccRCC compared to NAT. In the validation cohort, high BCL9 levels were associated with shorter progression-free survival (PFS) but not OS, while high TPX2 levels correlated with shorter overall survival (OS) but not PFS. Pathway analysis linked BCL9 to Wnt signaling and TPX2 to cell cycle regulation. Elevated BCL9 and TPX2 are associated with poor prognosis in ccRCC. These proteins are potential prognostic markers and therapeutic targets.