Identification of novel lncRNA prognostic biomarkers and their associated ceRNAs in bladder urothelial carcinoma

Abstract

AbstractBladder urothelial carcinoma (BUCA) is a common malignant tumor with a high rate of metastasis and recurrence. The lack of specific and sensitive biomarkers for the prognostic assessment makes it important to seek alternatives. Recent studies have demonstrated that long noncoding RNAs (lncRNAs) function as competitive endogenous RNAs (ceRNAs) and play an important role in BUCA prognosis. Therefore, this study aimed to establish a prognosis‐related lncRNAs–microRNAs (miRNAs)–messenger RNA (mRNA) (pceRNA) network and identify novel prognostic biomarkers. Integrated weighted coexpression analysis, functional clustering, and ceRNA network were used for the prognostic assessment of BUCA. The transcriptome sequencing datasets of lncRNA, miRNA, and mRNA from The Cancer Genome Atlas database were used for the identification of key lncRNAs and construction of the lncRNAs expression signature for prognostic prediction of BUCA patients. Then, 14 differentially expressed lncRNAs (DE‐lncRNAs) were identified as candidate prognostic RNAs based on the ceRNAs network and functional clustering. In the Cox regression analysis, two (AC008676.1 and ADAMTS9‐AS1) of all DE‐lncRNAs were significantly associated with overall survival (OS) of BUCA patients. This two DE‐lncRNA signature was significantly correlated with OS and was an independent prognostic factor, which was confirmed in an independent dataset of GSE216037. Moreover, we constructed the pceRNA network that includes 2 DE‐lncRNAs, 9 DE‐miRNAs, and 10 DE‐mRNAs. Pathway enrichment analysis showed that AC008676.1 and ADAMTS9‐AS1 are involved in several cancer‐related pathways such as proteoglycans in cancer and TGF‐beta signaling pathway. The novel‐identified DE‐lncRNA prognostic signature and the pceRNA network in this study will be valuable risk predictors and diagnostic markers for BUCA.