A five necroptosis-related lncRNA signature predicts the prognosis of bladder cancer and identifies hot or cold tumors.

Abstract

Bladder cancer (BC) is a leading cause of male cancer-related deaths globally. Immunotherapy is showing promise as a treatment option for BC. Numerous studies suggested that necroptosis and long noncoding RNAs (lncRNAs) were critical players in the development of cancers and interacting with cancer immunity. However, the prognostic value of necroptosis-related lncRNAs and their impact on immunotherapeutic response in patients with BC have yet to be well examined. Thus, this study aims to find new biomarkers for predicting prognosis and determining immune subtypes of BC to select appropriate patients from a heterogeneous population. The clinicopathology and transcriptome information from The Cancer Genome Atlas (TCGA) was downloaded, and coexpression analysis was performed to identify necroptosis-related lncRNAs. Then LASSO regression was employed to construct a prediction signature. The signature performance was evaluated by Kaplan-Meier (K-M) method, Time-dependent receiver operating characteristics (ROC). The functional enrichment, immune infiltration, immune checkpoint activation, and the half-maximal inhibitory concentration (IC50) of common drugs in risk groups were compared. The consensus clustering analysis based on lncRNAs associated with necroptosis was made to get 2 clusters to identify hot and cold tumors further. Lastly, the immune response between cold and hot tumors was discussed. In this study, a model containing 5 necroptosis-related lncRNAs was constructed. The risk score distribution of these lncRNAs was compared between low- and high-risk groups in the training, testing, and entire sets. K-M analysis showed that the low-risk patients had significantly better prognosis. The area under the ROC curve (AUC) for the 1-, 3-, and 5-year ROC curves in the entire sets were 0.690, 0.709, and 0.722, respectively. High-risk patients were enriched in lncRNAs related to tumor immunity and had better immune cell infiltration and immune checkpoint activation. Hot tumors and cold tumors were effectively distinguished by clusters 1 and cluster 2, respectively. We developed a necroptosis-related signature based on 5 prognostic lncRNAs, expected to become a new tool for evaluating the prognosis of patients with BC and classifying hot or cold tumors, thus facilitating the development of precision therapy for BC.