Abstract 5397: Gene signatures for predicting patients with aggressive type of bladder cancer and shorter survivals

Abstract

Abstract Bladder cancer is frequently associated with high recurrence and metastasis. With the success of cancer genome project in bladder cancer, we aimed to discover novel cancer drivers in muscle-invasive bladder cancer (MIBC), the most aggressive type of bladder cancer. A total of 155 genes were filtered out using RNAseq data from the TCGA cohort (n = 367), which are overexpressed (Z scores > 2.0) in more than 5% patients and correlated with poor overall survivals by Cox regression (p-value < 0.05) and FDR correction (q-value < 0.05). Using a unique HD-MAC (high-dimensional analysis of molecular alterations in cancer) algorithm developed by our team, 25 genes were further selected which show statistical significances as independent prognosis biomarkers for shorter overall survivals. Through clinical association study (including tumor stage, lymph node invasion, angiogenesis, and metastasis) by using CGDSR (Cancer Genomics Data Server in R), five most significant genes were further filtered which can be validated by another cohort (GSE13507). Although those genes show no direct gene-gene interactions, gene set enrichment analysis (GSEA) revealed common pathways governed by those driver genes, including cancer-related signaling, glycome alterations for TME remodeling, regulation in cell death, glutamate & neuronal signaling, and ER-Golgi transportation. The above findings can be also confirmed at the protein levels by IHC staining. In this study, how those key genes assist cell survival under nutrition crisis and their impacts on aggressive behaviors of bladder cancer will be discussed. Citation Format: Jim Jinn-Chyuan Sheu, Bo-Chen Lin, Oscar Yang, Chung Chang. Gene signatures for predicting patients with aggressive type of bladder cancer and shorter survivals [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5397.