A New Strategy to Authenticate Prognosis and Tumor Immunity Model Based on Cancer-Associated Fibroblasts lncRNA in Bladder Cancer

Abstract

There is growing evidence indicating that long noncoding RNAs (lncRNAs) play a pivotal role in regulating both cancer immunity and the cancer microenvironment. Specifically, cancer-associated fibroblasts (CAFs) have been found to have a significant impact on a variety of tumor types. However, the specific lncRNAs associated with CAFs have not yet been thoroughly studied in the context of bladder cancer. This study examined specific lncRNAs derived from TCGA data for the bladder tumor immune microenvironment (TME). Through our analysis, we identified 67 fibroblast-specific lncRNAs (referred to as FIBLnc), and further identified ten gene signatures that include RGS5, EPB41L4A-AS1, SNHG5, MAGI2-AS3, PVT1, EMX2OS, NEAT1, DLEU1, TMEM99, and A1BG-AS1. To establish the robustness of our findings, we also analyzed the gene expression profiles in the GSE13507, GSE19915, GSE31684, GSE48276, and GSE48277A datasets. The results from these datasets, along with the TCGA dataset, were highly accurate in detecting differences in overall survival using the FIBLnc signatures. In functional analysis, FIBLnc revealed its association with immune checkpoints and tumor progression. Furthermore, patients who were treated with anti-PD-1 or anti-CTLA4 could benefit from the FIBLnc score to predict their immunotherapy response. We further investigated the expression and prognostic power of lncRNAs EPB41L4A-AS1, TMEM99, and A1BG-AS1 in TCGA, bladder cell lines, and 24 paired tissues. Our results showed lower expression of EPB41L4A-AS1 and higher expression of TMEM99 and A1BG-AS1 in bladder malignancy, which correlated with a worse prognosis. Furthermore, we found that lncRNAEPB41L4A-AS1 could inhibit bladder cell carcinoma invasion in vitro. Overall, our study highlights the value of FIBLnc in assessing the immune environment status of individuals with bladder cancer and predicting their immunotherapy response. This investigation sheds light on the intricate processes involved in bladder cancer and underscores the importance of considering the FIBLnc score in the prognosis and management of this malignant tumor.