Kasperczak Michał, Kołodziejczak-Guglas Iga, Kasperczak Filip, Wiznerowicz Maciej, Antczak Andrzej
Department of Urology, J. Struś Hospital in Poznań, Szwajcarska 3, 61-285 Poznan, Poland.
International Institute for Molecular Oncology, 60-203 Poznan, Poland.
Int J Mol Sci. 2025 Apr 26;26(9):4114. doi: 10.3390/ijms26094114.
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.
透明细胞肾细胞癌（ccRCC）是一种预后较差且治疗选择有限的肾癌。识别新的预后标志物至关重要。本研究调查了参与癌症进展的两种蛋白质BCL9和TPX2预测患者预后的潜力。本研究使用液相色谱-串联质谱法（LC-MS/MS）分析了CPTAC队列（110例ccRCC和84例正常样本）的蛋白质丰度数据。通过免疫组织化学（IHC）在一个独立队列（52例ccRCC样本）中对BCL9和TPX2进行了验证。根据IHC评分将患者分为高表达组和低表达组。进行了生存分析，并进行了Reactome通路富集分析。与正常样本相比，ccRCC中BCL9和TPX2显著上调。在验证队列中，高BCL9水平与较短的无进展生存期（PFS）相关，但与总生存期（OS）无关，而高TPX2水平与较短的总生存期（OS）相关，但与无进展生存期（PFS）无关。通路分析将BCL9与Wnt信号通路联系起来，将TPX2与细胞周期调控联系起来。BCL9和TPX2升高与ccRCC的不良预后相关。这些蛋白质是潜在的预后标志物和治疗靶点。
