Prognostic implications of necroptosis-related long noncoding RNA signatures in muscle-invasive bladder cancer

Background: Bladder cancer (BLCA) is the sixth most common cancer in men, with an increasing incidence of morbidity and mortality. Necroptosis is a type of programmed cell death and plays a critical role in the biological processes of bladder cancer (BLCA). However, current studies focusing on long noncoding RNA (lncRNA) and necroptosis in cancer are limited, and there is no research about necroptosis-related lncRNAs (NRLs) in BLCA. Methods: We obtained the RNA-seq data and corresponding clinical information of BLCA from The Cancer Genome Atlas (TCGA) database. The seven determined prognostic NLRs were analyzed by several methods and verified by RT-qPCR. Then, a risk signature was established based on the aforementioned prognostic NLRs. To identify it, we evaluated its prognostic value by Kaplan-Meier (K-M) survival curve and receiver operating characteristics (ROC) curve analysis. Moreover, the relationships between risk signature and clinical features, functional enrichment, immune landscape, and drug resistance were explored as well. Results: We constructed a signature based on seven defined NLRs (HMGA2-AS1, LINC02489, ETV7-AS1, EMSLR, AC005954.1, STAG3L5P-PVRIG2P-PILRB, and LINC02178). Patients in the low-risk cohort had longer survival times than those in the high-risk cohort, and the area under the ROC curve (AUC) value of risk signature was higher than other clinical variables. Functional analyses, the infiltrating level of immune cells and functions, ESTIMATE score, and immune checkpoint analysis all indicated that the high-risk group was in a relatively immune-activated state. In terms of treatments, patients in the high-risk group were more sensitive to immunotherapy, especially anti-PD1/PD-L1 immunotherapy and conventional chemotherapy. Conclusion: The novel NLR signature acts as an invaluable tool for predicting prognosis, immune microenvironment, and drug resistance in muscle-invasive bladder cancer (MIBC) patients.